rs2061776

Variant names:

• chr19-8137489-C-T
• rs2061776
• NM_032447.5:c.1201+652G>A

Variant summary

Our verdict is Benign. The variant received -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
• 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 -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 rank	MANE	Protein	UniProt
FBN3	NM_032447.5	c.1201+652G>A		intron_variant	Intron 10 of 63	ENST00000600128.6	NP_115823.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBN3	ENST00000600128.6	c.1201+652G>A		intron_variant	Intron 10 of 63	1	NM_032447.5	ENSP00000470498.1
FBN3	ENST00000270509.6	c.1201+652G>A		intron_variant	Intron 9 of 62	1		ENSP00000270509.2
FBN3	ENST00000601739.5	c.1201+652G>A		intron_variant	Intron 10 of 63	1		ENSP00000472324.1
FBN3	ENST00000651877.1	c.1327+652G>A		intron_variant	Intron 10 of 63			ENSP00000498507.1

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

African (AFR) AF: 0.256 AC: 10612 AN: 41416

American (AMR) AF: 0.135 AC: 2061 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 416 AN: 3468

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5176

South Asian (SAS) AF: 0.0760 AC: 366 AN: 4818

European-Finnish (FIN) AF: 0.163 AC: 1724 AN: 10550

Middle Eastern (MID) AF: 0.113 AC: 33 AN: 292

European-Non Finnish (NFE) AF: 0.166 AC: 11294 AN: 67970

Other (OTH) AF: 0.152 AC: 318 AN: 2098

Alfa AF: 0.161 Hom.: 3747

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
PhyloP100		-0.13
Mutation Taster		=100/0	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: rs2061776; hg19: chr19-8202373;