2-157781963-C-T

Variant names:

• chr2-157781963-C-T
• rs10933441
• NM_001111067.4:c.68-1363G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001111067.4(ACVR1):​c.68-1363G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0767 in 152,228 control chromosomes in the GnomAD database, including 826 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 0.077 (826 hom., cov: 32)
• Consequence: ACVR1 NM_001111067.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.645
• Publications: 6 publications found

Genes affected

ACVR1 (HGNC:171): (activin A receptor type 1) Activins are dimeric growth and differentiation factors which belong to the transforming growth factor-beta (TGF-beta) superfamily of structurally related signaling proteins. Activins signal through a heteromeric complex of receptor serine kinases which include at least two type I ( I and IB) and two type II (II and IIB) receptors. These receptors are all transmembrane proteins, composed of a ligand-binding extracellular domain with cysteine-rich region, a transmembrane domain, and a cytoplasmic domain with predicted serine/threonine specificity. Type I receptors are essential for signaling; and type II receptors are required for binding ligands and for expression of type I receptors. Type I and II receptors form a stable complex after ligand binding, resulting in phosphorylation of type I receptors by type II receptors. This gene encodes activin A type I receptor which signals a particular transcriptional response in concert with activin type II receptors. Mutations in this gene are associated with fibrodysplasia ossificans progressive. [provided by RefSeq, Jul 2008]

ACVR1 Gene-Disease associations (from GenCC):

• fibrodysplasia ossificans progressiva

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, ClinGen, Orphanet
• congenital heart disease

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACVR1	NM_001111067.4	c.68-1363G>A		intron_variant	Intron 3 of 10	ENST00000434821.7	NP_001104537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACVR1	ENST00000434821.7	c.68-1363G>A		intron_variant	Intron 3 of 10	1	NM_001111067.4	ENSP00000405004.1

Frequencies

GnomAD3 genomes AF: 0.0768 AC: 11684 AN: 152110 Hom.: 829 Cov.: 32

Gnomad AFR AF: 0.0193

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.0664

Gnomad ASJ AF: 0.0798

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0815

Gnomad OTH AF: 0.0770

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

GnomAD4 genome AF: 0.0767 AC: 11683 AN: 152228 Hom.: 826 Cov.: 32 AF XY: 0.0806 AC XY: 6001 AN XY: 74422

African (AFR) AF: 0.0193 AC: 801 AN: 41548

American (AMR) AF: 0.0661 AC: 1011 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0798 AC: 277 AN: 3470

East Asian (EAS) AF: 0.388 AC: 2002 AN: 5154

South Asian (SAS) AF: 0.103 AC: 495 AN: 4820

European-Finnish (FIN) AF: 0.124 AC: 1314 AN: 10596

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0814 AC: 5540 AN: 68018

Other (OTH) AF: 0.0814 AC: 172 AN: 2114

Alfa AF: 0.0727 Hom.: 438

Bravo AF: 0.0709

Asia WGS AF: 0.219 AC: 757 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.3
DANN	Benign	0.65
PhyloP100		0.65
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: rs10933441; hg19: chr2-158638475;