19-8094525-G-T

Variant names:

• chr19-8094525-G-T
• rs7245552
• NM_032447.5:c.5826C>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_032447.5(FBN3):​c.5826C>A​(p.Pro1942Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 1,612,836 control chromosomes in the GnomAD database, including 340,611 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P1942P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.61 (29223 hom., cov: 33)
  • Exomes 𝑓: 0.65 (311388 hom.)
• Consequence: FBN3 NM_032447.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.12
• Publications: 22 publications found

Genes affected

FBN3 (HGNC:18794): (fibrillin 3) This gene encodes a memebr of the fibrillin protein family. Fibrillins are extracellular matrix molecules that assemble into microfibrils in many connective tissues. This gene is most highly expressed in fetal tissues and its protein product is localized to extracellular microfibrils of developing skeletal elements, skin, lung, kidney, and skeletal muscle. This gene is potentially involved in Weill-Marchesani syndrome. [provided by RefSeq, Mar 2016]

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.097).
• BP6: Variant 19-8094525-G-T is Benign according to our data. Variant chr19-8094525-G-T is described in ClinVar as Benign. ClinVar VariationId is 1277303.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.12 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBN3	NM_032447.5	c.5826C>A	p.Pro1942Pro	synonymous_variant	Exon 47 of 64	ENST00000600128.6	NP_115823.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBN3	ENST00000600128.6	c.5826C>A	p.Pro1942Pro	synonymous_variant	Exon 47 of 64	1	NM_032447.5	ENSP00000470498.1
FBN3	ENST00000270509.6	c.5826C>A	p.Pro1942Pro	synonymous_variant	Exon 46 of 63	1		ENSP00000270509.2
FBN3	ENST00000601739.5	c.5826C>A	p.Pro1942Pro	synonymous_variant	Exon 47 of 64	1		ENSP00000472324.1
FBN3	ENST00000651877.1	c.5952C>A	p.Pro1984Pro	synonymous_variant	Exon 47 of 64			ENSP00000498507.1

Frequencies

GnomAD3 genomes AF: 0.608 AC: 92455 AN: 152032 Hom.: 29191 Cov.: 33

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.712

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.899

Gnomad SAS AF: 0.791

Gnomad FIN AF: 0.735

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.592

GnomAD2 exomes AF: 0.685 AC: 171619 AN: 250590 AF XY: 0.686

Gnomad AFR exome AF: 0.446

Gnomad AMR exome AF: 0.806

Gnomad ASJ exome AF: 0.634

Gnomad EAS exome AF: 0.894

Gnomad FIN exome AF: 0.722

Gnomad NFE exome AF: 0.623

Gnomad OTH exome AF: 0.657

GnomAD4 exome AF: 0.648 AC: 947212 AN: 1460686 Hom.: 311388 Cov.: 41 AF XY: 0.652 AC XY: 473602 AN XY: 726610

African (AFR) AF: 0.439 AC: 14690 AN: 33462

American (AMR) AF: 0.796 AC: 35544 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 16439 AN: 26104

East Asian (EAS) AF: 0.908 AC: 36043 AN: 39678

South Asian (SAS) AF: 0.772 AC: 66574 AN: 86190

European-Finnish (FIN) AF: 0.716 AC: 38214 AN: 53368

Middle Eastern (MID) AF: 0.605 AC: 3479 AN: 5746

European-Non Finnish (NFE) AF: 0.628 AC: 697531 AN: 1111136

Other (OTH) AF: 0.641 AC: 38698 AN: 60330

GnomAD4 genome AF: 0.608 AC: 92527 AN: 152150 Hom.: 29223 Cov.: 33 AF XY: 0.618 AC XY: 46001 AN XY: 74388

African (AFR) AF: 0.451 AC: 18708 AN: 41502

American (AMR) AF: 0.713 AC: 10903 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 2139 AN: 3470

East Asian (EAS) AF: 0.899 AC: 4654 AN: 5176

South Asian (SAS) AF: 0.792 AC: 3821 AN: 4824

European-Finnish (FIN) AF: 0.735 AC: 7774 AN: 10578

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.625 AC: 42486 AN: 67988

Other (OTH) AF: 0.594 AC: 1256 AN: 2114

Alfa AF: 0.615 Hom.: 89790

Bravo AF: 0.596

Asia WGS AF: 0.804 AC: 2794 AN: 3478

EpiCase AF: 0.617

EpiControl AF: 0.616

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 21, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	5.1
DANN	Benign	0.56
PhyloP100		-3.1
Mutation Taster		=94/6	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7245552; hg19: chr19-8159409; COSMIC: COSV54460147; COSMIC: COSV54460147;