rs8102892

chr19-8086285-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_032447.5(FBN3):c.6795C>T(p.Asn2265=) 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:2
• Conservation: PhyloP100: -1.32

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

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
FBN3	NM_032447.5	c.6795C>T	p.Asn2265=	synonymous_variant	55/64	ENST00000600128.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBN3	ENST00000600128.6	c.6795C>T	p.Asn2265=	synonymous_variant	55/64	1	NM_032447.5
FBN3	ENST00000270509.6	c.6795C>T	p.Asn2265=	synonymous_variant	54/63	1
FBN3	ENST00000601739.5	c.6795C>T	p.Asn2265=	synonymous_variant	55/64	1
FBN3	ENST00000651877.1	c.6921C>T	p.Asn2307=	synonymous_variant	55/64			P1

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

GnomAD3 exomes AF: 0.0107 AC: 2674 AN: 249440 Hom.: 149 AF XY: 0.00798 AC XY: 1077 AN XY: 134990

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 SAS exome AF: 0.00161

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

Gnomad4 AFR exome AF: 0.136

Gnomad4 AMR exome AF: 0.00785

Gnomad4 ASJ exome AF: 0.0134

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00193

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000220

Gnomad4 OTH exome AF: 0.00910

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

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.0132

Gnomad4 ASJ AF: 0.0127

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000633

Gnomad4 OTH AF: 0.0318

Alfa AF: 0.00827 Hom.: 92

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

FBN3-related condition Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 19, 2019

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). -

not provided 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	-0.60
Cadd	Benign	0.11
Dann	Benign	0.92

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

Publications

LitVar

Other links and lift over

dbSNP: rs8102892; hg19: chr19-8151169;