2-157856026-C-T

Variant summary

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

The NM_001111067.4(ACVR1):c.-183+19770G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 151,508 control chromosomes in the GnomAD database, including 31,702 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 0.60 (31702 hom., cov: 29)
• Consequence: ACVR1 NM_001111067.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.11

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACVR1	NM_001111067.4	c.-183+19770G>A		intron_variant		ENST00000434821.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACVR1	ENST00000434821.7	c.-183+19770G>A		intron_variant		1	NM_001111067.4	P4

Frequencies

GnomAD3 genomes AF: 0.601 AC: 91056 AN: 151390 Hom.: 31704 Cov.: 29

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.735

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.763

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.768

Gnomad OTH AF: 0.634

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

GnomAD4 genome AF: 0.601 AC: 91061 AN: 151508 Hom.: 31702 Cov.: 29 AF XY: 0.603 AC XY: 44632 AN XY: 74048

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.746

Gnomad4 ASJ AF: 0.735

Gnomad4 EAS AF: 0.495

Gnomad4 SAS AF: 0.585

Gnomad4 FIN AF: 0.763

Gnomad4 NFE AF: 0.768

Gnomad4 OTH AF: 0.629

Alfa AF: 0.737 Hom.: 53177

Bravo AF: 0.583

Asia WGS AF: 0.499 AC: 1738 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.017
Dann	Benign	0.62

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: rs4664901; hg19: chr2-158712538;