rs201590889

Positions:

• chr11-65553761-G-A
• chr11-65553761-G-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001130144.3(LTBP3):​c.804C>T​(p.Pro268=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0164 in 1,573,436 control chromosomes in the GnomAD database, including 282 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (15 hom., cov: 31)
  • Exomes 𝑓: 0.017 (267 hom.)
• Consequence: LTBP3 NM_001130144.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.49

Genes affected

LTBP3 (HGNC:6716): (latent transforming growth factor beta binding protein 3) The protein encoded by this gene forms a complex with transforming growth factor beta (TGF-beta) proteins and may be involved in their subcellular localization. Activation of this complex requires removal of the encoded binding protein. This protein also may play a structural role in the extracellular matrix. Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 11-65553761-G-A is Benign according to our data. Variant chr11-65553761-G-A is described in ClinVar as [Benign]. Clinvar id is 464026.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-65553761-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-1.49 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0119 (1805/151936) while in subpopulation NFE AF= 0.0183 (1243/67906). AF 95% confidence interval is 0.0175. There are 15 homozygotes in gnomad4. There are 845 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 15 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LTBP3	NM_001130144.3	c.804C>T	p.Pro268=	synonymous_variant	3/28	ENST00000301873.11
LTBP3	NM_021070.4	c.804C>T	p.Pro268=	synonymous_variant	3/27
LTBP3	NM_001164266.1	c.453C>T	p.Pro151=	synonymous_variant	3/27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LTBP3	ENST00000301873.11	c.804C>T	p.Pro268=	synonymous_variant	3/28	2	NM_001130144.3	P1

Frequencies

GnomAD3 genomes AF: 0.0119 AC: 1805 AN: 151818 Hom.: 15 Cov.: 31

Gnomad AFR AF: 0.00365

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00321

Gnomad ASJ AF: 0.00577

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00167

Gnomad FIN AF: 0.0298

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0183

Gnomad OTH AF: 0.00815

GnomAD3 exomes AF: 0.0127 AC: 2296 AN: 180764 Hom.: 17 AF XY: 0.0128 AC XY: 1272 AN XY: 99652

Gnomad AFR exome AF: 0.00352

Gnomad AMR exome AF: 0.00289

Gnomad ASJ exome AF: 0.00583

Gnomad EAS exome AF: 0.000740

Gnomad SAS exome AF: 0.00134

Gnomad FIN exome AF: 0.0381

Gnomad NFE exome AF: 0.0220

Gnomad OTH exome AF: 0.0119

GnomAD4 exome AF: 0.0169 AC: 24016 AN: 1421500 Hom.: 267 Cov.: 34 AF XY: 0.0164 AC XY: 11580 AN XY: 704924

Gnomad4 AFR exome AF: 0.00263

Gnomad4 AMR exome AF: 0.00282

Gnomad4 ASJ exome AF: 0.00558

Gnomad4 EAS exome AF: 0.000207

Gnomad4 SAS exome AF: 0.00188

Gnomad4 FIN exome AF: 0.0358

Gnomad4 NFE exome AF: 0.0196

Gnomad4 OTH exome AF: 0.0116

GnomAD4 genome AF: 0.0119 AC: 1805 AN: 151936 Hom.: 15 Cov.: 31 AF XY: 0.0114 AC XY: 845 AN XY: 74240

Gnomad4 AFR AF: 0.00364

Gnomad4 AMR AF: 0.00321

Gnomad4 ASJ AF: 0.00577

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.00167

Gnomad4 FIN AF: 0.0298

Gnomad4 NFE AF: 0.0183

Gnomad4 OTH AF: 0.00806

Alfa AF: 0.00753 Hom.: 2

Bravo AF: 0.00986

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Brachyolmia-amelogenesis imperfecta syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.72
DANN	Benign	0.89

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs201590889; hg19: chr11-65321232; COSMIC: COSV57238497; COSMIC: COSV57238497;