rs1372115

chr2-157820987-T-C

Variant summary

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

The NM_001111067.4(ACVR1):c.-182-2428A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 152,120 control chromosomes in the GnomAD database, including 36,954 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 0.63 (36954 hom., cov: 32)
• Consequence: ACVR1 NM_001111067.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.945

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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACVR1	NM_001111067.4	c.-182-2428A>G		intron_variant		ENST00000434821.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACVR1	ENST00000434821.7	c.-182-2428A>G		intron_variant		1	NM_001111067.4	P4

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96368 AN: 152002 Hom.: 36948 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.768

Gnomad ASJ AF: 0.817

Gnomad EAS AF: 0.796

Gnomad SAS AF: 0.826

Gnomad FIN AF: 0.856

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.815

Gnomad OTH AF: 0.668

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

GnomAD4 genome AF: 0.634 AC: 96375 AN: 152120 Hom.: 36954 Cov.: 32 AF XY: 0.641 AC XY: 47699 AN XY: 74366

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.768

Gnomad4 ASJ AF: 0.817

Gnomad4 EAS AF: 0.797

Gnomad4 SAS AF: 0.827

Gnomad4 FIN AF: 0.856

Gnomad4 NFE AF: 0.815

Gnomad4 OTH AF: 0.669

Alfa AF: 0.712 Hom.: 5331

Bravo AF: 0.598

Asia WGS AF: 0.768 AC: 2667 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.27
Dann	Benign	0.73

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: rs1372115; hg19: chr2-158677499;