15-48520779-C-T

Variant names:

• chr15-48520779-C-T
• rs146726731
• NM_000138.5:c.1027G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 5P and 1B. PM1 PP2 PP3_Moderate BP6

The NM_000138.5(FBN1):​c.1027G>A​(p.Gly343Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000205 in 1,614,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/19 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. G343G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00020 (0 hom.)
• Consequence: FBN1 NM_000138.5 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:9 B:10
• Conservation: PhyloP100: 7.71
• Publications: 16 publications found

Genes affected

FBN1 (HGNC:3603): (fibrillin 1) This gene encodes a member of the fibrillin family of proteins. The encoded preproprotein is proteolytically processed to generate two proteins including the extracellular matrix component fibrillin-1 and the protein hormone asprosin. Fibrillin-1 is an extracellular matrix glycoprotein that serves as a structural component of calcium-binding microfibrils. These microfibrils provide force-bearing structural support in elastic and nonelastic connective tissue throughout the body. Asprosin, secreted by white adipose tissue, has been shown to regulate glucose homeostasis. Mutations in this gene are associated with Marfan syndrome and the related MASS phenotype, as well as ectopia lentis syndrome, Weill-Marchesani syndrome, Shprintzen-Goldberg syndrome and neonatal progeroid syndrome. [provided by RefSeq, Apr 2016]

FBN1 Gene-Disease associations (from GenCC):

• familial thoracic aortic aneurysm and aortic dissection

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• Marfan syndrome

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen, G2P, PanelApp Australia, Orphanet, Ambry Genetics
• Acromicric dysplasia

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics
• progeroid and marfanoid aspect-lipodystrophy syndrome

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
• stiff skin syndrome

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Weill-Marchesani syndrome 2, dominant

  Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• geleophysic dysplasia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• isolated ectopia lentis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• neonatal Marfan syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Weill-Marchesani syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• ectopia lentis 1, isolated, autosomal dominant

  Inheritance: AD Classification: LIMITED Submitted by: G2P
• Shprintzen-Goldberg syndrome

  Inheritance: AD, Unknown Classification: LIMITED, NO_KNOWN Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM1: In a hotspot region, there are 4 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 10 uncertain in NM_000138.5
• PP2: Missense variant in the FBN1 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 1311 curated pathogenic missense variants (we use a threshold of 10). The gene has 112 curated benign missense variants. Gene score misZ: 5.0644 (above the threshold of 3.09). Trascript score misZ: 8.1787 (above the threshold of 3.09). GenCC associations: The gene is linked to Marfan syndrome, Weill-Marchesani syndrome 2, dominant, progeroid and marfanoid aspect-lipodystrophy syndrome, geleophysic dysplasia, Shprintzen-Goldberg syndrome, stiff skin syndrome, familial thoracic aortic aneurysm and aortic dissection, isolated ectopia lentis, ectopia lentis 1, isolated, autosomal dominant, Acromicric dysplasia, neonatal Marfan syndrome, Weill-Marchesani syndrome.
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.91
• BP6: Variant 15-48520779-C-T is Benign according to our data. Variant chr15-48520779-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 161244.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBN1	NM_000138.5	c.1027G>A	p.Gly343Arg	missense_variant	Exon 10 of 66	ENST00000316623.10	NP_000129.3
FBN1	NM_001406716.1	c.1027G>A	p.Gly343Arg	missense_variant	Exon 9 of 65		NP_001393645.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBN1	ENST00000316623.10	c.1027G>A	p.Gly343Arg	missense_variant	Exon 10 of 66	1	NM_000138.5	ENSP00000325527.5
FBN1	ENST00000559133.6	n.1027G>A		non_coding_transcript_exon_variant	Exon 10 of 67	1		ENSP00000453958.2
FBN1	ENST00000674301.2	n.1027G>A		non_coding_transcript_exon_variant	Exon 10 of 68			ENSP00000501333.2
FBN1	ENST00000537463.6	n.636+16932G>A		intron_variant	Intron 7 of 30	5		ENSP00000440294.2

Frequencies

GnomAD3 genomes AF: 0.000223 AC: 34 AN: 152144 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000187 AC: 47 AN: 251314 AF XY: 0.000214

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000434

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000255

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000203 AC: 297 AN: 1461878 Hom.: 0 Cov.: 31 AF XY: 0.000197 AC XY: 143 AN XY: 727242

African (AFR) AF: 0.000149 AC: 5 AN: 33478

American (AMR) AF: 0.000402 AC: 18 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000234 AC: 260 AN: 1112006

Other (OTH) AF: 0.000215 AC: 13 AN: 60394

GnomAD4 genome AF: 0.000223 AC: 34 AN: 152262 Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16 AN XY: 74454

African (AFR) AF: 0.0000722 AC: 3 AN: 41540

American (AMR) AF: 0.000327 AC: 5 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000353 AC: 24 AN: 68016

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000354 Hom.: 0

Bravo AF: 0.000306

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000157 AC: 19

EpiCase AF: 0.000218

EpiControl AF: 0.000296

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:9 Benign:10

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Uncertain:5

Mar 27, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The FBN1 c.1027G>A; p.Gly343Arg variant (rs146726731; ClinVar Variation ID: 161244) has been reported in multiple cohorts of individuals with suspected or confirmed Marfan syndrome (Tjeldhorn 2006, Rand-Hendriksen 2007, Viveiro 2013, Becerra-Munoz 2018, Fernandez-Alvarez 2022), including a purported de novo observation (Fernandez-Alvarez 2022). However, this variant was identified alongside other pathogenic variation in other genes in affected patients (Grond-Ginsbach 2017 and Arbustini 2017), and failed to co-segregate with disease in two cousins affected with cervical artery dissection (Grond-Ginsbach 2017). Additionally, this variant is also found in the non-Finnish European population with an allele frequency of 0.03% (33/129,054 alleles) in the Genome Aggregation Database (v2.1.1) and reported in several additional studies of variant in the general population (Amendola 2015, Groth 2016, Olfson 2015, Yang 2014). This variant is located in the TGF-beta binding (TB) domain of FBN1 (not in an EGF domain), though computational analyses predict that this variant is deleterious (REVEL: 0.863). Due to conflicting information, the clinical significance of this variant is uncertain at this time. References: Amendola et al. Actionable exomic incidental findings in 6503 participants: challenges of variant classification. Genome Res. 2015; 25(3): 305-315. PMID: 25637381 Arbustini E et al. Reply: A Distinct Cardiomyopathy: HCN4 Syndrome Comprising Myocardial Noncompaction, Bradycardia, Mitral Valve Defects, and Aortic Dilation. J Am Coll Cardiol. 2017 Mar 7;69(9):1210-1211. PMID: 28254189. Becerra-Munoz VM et al The importance of genotype-phenotype correlation in the clinical management of Marfan syndrome. Orphanet J Rare Dis. 2018 Jan 22;13(1):16. PMID: 29357934 Fernandez-Alvarez P et al. A systematic study and literature review of parental somatic mosaicism of FBN1 pathogenic variants in Marfan syndrome. J Med Genet. 2022 Jun;59(6):605-612. PMID: 33910934. Grond-Ginsbach C et al. Next generation sequencing analysis of patients with familial cervical artery dissection. Eur Stroke J. 2017 Jun;2(2):137-143. PMID: 31008308 Groth et al. Difficulties in diagnosing Marfan syndrome using current FBN1 databases. Genet Med. 2016; 18(1): 98-102. PMID: 25812041 Olfson et al. Identification of Medically Actionable Secondary Findings in the 1000 Genomes. PLoS One. 2015; 10(9): e0135193. PMID: 26332594 Rand-Hendriksen S et al. Search for correlations between FBN1 genotype and complete Ghent phenotype in 44 unrelated Norwegian patients with Marfan syndrome. Am J Med Genet A. 2007 Sep 1;143A(17):1968-77. PMID: 17663468. Tjeldhorn et al. Rapid and efficient FBN1 mutation detection using automated sample preparation and direct sequencing as the primary strategy. Genet Test. 2006; 10(4): 258-264. PMID: 17253931 Viveiro et al. Spontaneous pneumothorax as manifestation of Marfan syndrome. BMJ Case Rep. 2013; 2013. PMID: 24311428 Yang et al. New population-based exome data question the pathogenicity of some genetic variants previously associated with Marfan syndrome. BMC Genet. 2014; 15:74. PMID: 24941995 -

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Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Nov 01, 2020

CeGaT Center for Human Genetics Tuebingen

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 17, 2024

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Published in association with confirmed or suspected Marfan syndrome as well as carotid artery dissection or thoracic aortic aneurysm; however, one individual was found to harbor another variant that likely contributed to the phenotype, and an affected relative of a different proband was reported to be absent for this variant (PMID: 17253931, 17663468, 24311428, 26684006, 31008308, 29357934, 36889877); Does not affect a cysteine or calcium-binding residue within an EGF-like domain or a TGF-binding protein domain of the FBN1 gene; cysteine substitutions in the EGF-like domains represent the majority of pathogenic missense changes associated with FBN1-related disorders (PMID: 12938084); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25637381, 27647783, 24311428, 24941995, 26332594, 25812041, 26684006, 28254189, 29357934, 30122538, 17663468, 31008308, 17253931, 33910934, 31322791, 35886052, 36889877, 12938084) -

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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Marfan syndrome Uncertain:2 Benign:1

Feb 05, 2024

All of Us Research Program, National Institutes of Health

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This missense variant replaces glycine with arginine at codon 343 of the FBN1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in a few individuals suspected of having Marfan syndrome (PMID: 17253931, 17663468, 24311428). This variant has been reported in an individual affected with cervical artery dissection (PMID: 31008308); this individual also carried a pathogenic variant in the COL3A1 gene. This variant has been identified in 52/282706 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. -

Jun 01, 2014

CSER _CC_NCGL, University of Washington

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: research

- -

May 30, 2018

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Familial thoracic aortic aneurysm and aortic dissection Uncertain:1 Benign:2

Mar 28, 2024

Color Diagnostics, LLC DBA Color Health

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 06, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The p.G343R variant (also known as c.1027G>A), located in coding exon 9 of the FBN1 gene, results from a G to A substitution at nucleotide position 1027. The glycine at codon 343 is replaced by arginine, an amino acid with dissimilar properties. This alteration was first reported in a cohort of 105 patients with suspected Marfan syndrome (MFS) (Tjeldhorn L et al. Genet. Test., 2006;10:258-64). Later, the same group reported that the individual carrying this alteration was diagnosed with MFS (Rand-Hendriksen S et al. Am. J. Med. Genet. A. 2007;143A:1968-77), and had increased FBN1 mRNA in fibroblasts (Tjeldhorn L et al. BMC Med. Genet. 2015;16:113). This alteration was also described in a patient with spontaneous pneumothorax and Marfanoid habitus, and was detected in two relatives reported to have MFS in another study (Viveiro C et al. BMJ Case Rep, 2013;2013; Becerra-Muñoz VM. Orphanet J Rare Dis. 2018;13(1):16). This variant co-occurred with an alteration in COL3A1 in a family with carotid artery dissection, where the current variant was absent in one affected relative (Grond-Ginsbach C et al. Eur Stroke J, 2017 Jun;2:137-143). In addition, this variant has been seen in an exome cohort, but cardiovascular history was not provided (Amendola LM et al. Genome Res., 2015 Mar;25:305-15). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -

May 30, 2018

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Connective tissue disorder Uncertain:1

Nov 01, 2016

Center for Human Genetics, Inc, Center for Human Genetics, Inc

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Aug 06, 2024

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: FBN1 c.1027G>A (p.Gly343Arg) results in a non-conservative amino acid change located in the TB domain (IPR017878) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00019 in 251406 control chromosomes, predominantly at a frequency of 0.00043 within the Latino subpopulation in the gnomAD database. The observed variant frequency within Latino control individuals in the gnomAD database is approximately 4 fold of the estimated maximal expected allele frequency for a pathogenic variant in FBN1 causing Aortopathy phenotype (0.00011). c.1027G>A has been reported in the literature in individuals affected with Aortopathy or MFS without strong evidence for causality (Tjeldhorn_2006, Tjeldhorn_2015, Rand-Hendriksen_2007, Viveiro_2013, Grond-Ginsbach_2017, Becerra-Munoz_2018, Kasak_2019). These report(s) do not provide unequivocal conclusions about association of the variant with Aortopathy. Co-occurrences with other pathogenic variant(s) have been reported ( COL3A1 c.970G>A, p.G324S), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 17253931, 17663468, 24941995, 26332594, 25637381, 25812041, 24311428, 29357934, 31008308, 31322791, 26684006). ClinVar contains an entry for this variant (Variation ID: 161244). Based on the evidence outlined above, the variant was classified as likely benign. -

Stiff skin syndrome Benign:1

May 30, 2018

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Weill-Marchesani syndrome Benign:1

May 30, 2018

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Geleophysic dysplasia Benign:1

May 30, 2018

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Acromicric dysplasia Benign:1

May 30, 2018

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Marfan syndrome;C4707243:Familial thoracic aortic aneurysm and aortic dissection Benign:1

Dec 23, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Ectopia lentis 1, isolated, autosomal dominant Benign:1

May 30, 2018

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.51
CADD	Pathogenic	28
DANN	Pathogenic	1.0
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Pathogenic	0.40	D
MetaRNN	Pathogenic	0.91	D
MetaSVM	Pathogenic	0.92	D
PhyloP100		7.7
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-7.0	D
REVEL	Pathogenic	0.86
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.045	D
Vest4		0.97
MutPred		0.85		Gain of catalytic residue at G343 (P = 0.0477);
MVP		0.97
MPC		1.6
ClinPred		0.75	D
GERP RS		5.7
Mutation Taster		=2/98	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs146726731; hg19: chr15-48812976;