rs8102892

Variant names:

• chr19-8086285-G-A
• rs8102892
• NM_032447.5:c.6795C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_032447.5(FBN3):​c.6795C>T​(p.Asn2265Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00739 in 1,612,238 control chromosomes in the GnomAD database, including 677 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.037 (360 hom., cov: 30)
  • Exomes 𝑓: 0.0043 (317 hom.)
• Consequence: FBN3 NM_032447.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.32
• Publications: 5 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 19-8086285-G-A is Benign according to our data. Variant chr19-8086285-G-A is described in ClinVar as Benign. ClinVar VariationId is 1562427.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.32 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBN3	NM_032447.5	c.6795C>T	p.Asn2265Asn	synonymous_variant	Exon 55 of 64	ENST00000600128.6	NP_115823.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBN3	ENST00000600128.6	c.6795C>T	p.Asn2265Asn	synonymous_variant	Exon 55 of 64	1	NM_032447.5	ENSP00000470498.1
FBN3	ENST00000270509.6	c.6795C>T	p.Asn2265Asn	synonymous_variant	Exon 54 of 63	1		ENSP00000270509.2
FBN3	ENST00000601739.5	c.6795C>T	p.Asn2265Asn	synonymous_variant	Exon 55 of 64	1		ENSP00000472324.1
FBN3	ENST00000651877.1	c.6921C>T	p.Asn2307Asn	synonymous_variant	Exon 55 of 64			ENSP00000498507.1

Frequencies

GnomAD3 genomes AF: 0.0373 AC: 5666 AN: 151882 Hom.: 361 Cov.: 30

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0133

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000633

Gnomad OTH AF: 0.0321

GnomAD2 exomes AF: 0.0107 AC: 2674 AN: 249440 AF XY: 0.00798

Gnomad AFR exome AF: 0.135

Gnomad AMR exome AF: 0.00684

Gnomad ASJ exome AF: 0.0139

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000488

Gnomad OTH exome AF: 0.00560

GnomAD4 exome AF: 0.00427 AC: 6235 AN: 1460244 Hom.: 317 Cov.: 32 AF XY: 0.00383 AC XY: 2785 AN XY: 726474

African (AFR) AF: 0.136 AC: 4539 AN: 33360

American (AMR) AF: 0.00785 AC: 350 AN: 44612

Ashkenazi Jewish (ASJ) AF: 0.0134 AC: 348 AN: 26058

East Asian (EAS) AF: 0.00 AC: 0 AN: 39586

South Asian (SAS) AF: 0.00193 AC: 166 AN: 86146

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53326

Middle Eastern (MID) AF: 0.00677 AC: 39 AN: 5758

European-Non Finnish (NFE) AF: 0.000220 AC: 244 AN: 1111090

Other (OTH) AF: 0.00910 AC: 549 AN: 60308

GnomAD4 genome AF: 0.0374 AC: 5679 AN: 151994 Hom.: 360 Cov.: 30 AF XY: 0.0359 AC XY: 2667 AN XY: 74294

African (AFR) AF: 0.128 AC: 5315 AN: 41448

American (AMR) AF: 0.0132 AC: 202 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0127 AC: 44 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000633 AC: 43 AN: 67894

Other (OTH) AF: 0.0318 AC: 67 AN: 2108

Alfa AF: 0.0148 Hom.: 244

Bravo AF: 0.0427

Asia WGS AF: 0.00780 AC: 29 AN: 3476

EpiCase AF: 0.000820

EpiControl AF: 0.000656

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

FBN3-related disorder Benign:1

Feb 19, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.11
DANN	Benign	0.92
PhyloP100		-1.3
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs8102892; hg19: chr19-8151169;