rs2061776

chr19-8137489-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032447.5(FBN3):c.1201+652G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 151,950 control chromosomes in the GnomAD database, including 2,731 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (2731 hom., cov: 31)
• Consequence: FBN3 NM_032447.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.128

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBN3	NM_032447.5	c.1201+652G>A		intron_variant		ENST00000600128.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBN3	ENST00000600128.6	c.1201+652G>A		intron_variant		1	NM_032447.5
FBN3	ENST00000270509.6	c.1201+652G>A		intron_variant		1
FBN3	ENST00000601739.5	c.1201+652G>A		intron_variant		1
FBN3	ENST00000651877.1	c.1327+652G>A		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26922 AN: 151832 Hom.: 2731 Cov.: 31

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0763

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.153

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.177 AC: 26939 AN: 151950 Hom.: 2731 Cov.: 31 AF XY: 0.173 AC XY: 12885 AN XY: 74266

Gnomad4 AFR AF: 0.256

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.0760

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.152

Alfa AF: 0.158 Hom.: 2683

Bravo AF: 0.180

Asia WGS AF: 0.0490 AC: 170 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	1.5
Dann	Benign	0.42

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: rs2061776; hg19: chr19-8202373;