rs2033962

Variant names:

• chr2-157781929-A-C
• rs2033962
• NM_001111067.4:c.68-1329T>G

Your query was ambiguous. Multiple possible variants found:

• chr2-157781929-A-C
• chr2-157781929-A-G
• chr2-157781929-A-T

Variant summary

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

The NM_001111067.4(ACVR1):​c.68-1329T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 152,068 control chromosomes in the GnomAD database, including 49,785 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 0.81 (49785 hom., cov: 31)
• Consequence: ACVR1 NM_001111067.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0200
• Publications: 7 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: G2P, ClinGen, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001111067.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACVR1	NM_001111067.4	MANE Select	c.68-1329T>G		intron	N/A	NP_001104537.1	D3DPA4
	ACVR1	NM_001105.5		c.68-1329T>G		intron	N/A	NP_001096.1	D3DPA4
	ACVR1	NM_001347663.1		c.68-1329T>G		intron	N/A	NP_001334592.1	Q04771

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACVR1	ENST00000434821.7	TSL:1 MANE Select	c.68-1329T>G		intron	N/A	ENSP00000405004.1	Q04771
	ACVR1	ENST00000263640.7	TSL:1	c.68-1329T>G		intron	N/A	ENSP00000263640.3	Q04771
	ACVR1	ENST00000410057.6	TSL:1	c.68-1329T>G		intron	N/A	ENSP00000387127.2	Q04771

Frequencies

GnomAD3 genomes AF: 0.808 AC: 122736 AN: 151950 Hom.: 49738 Cov.: 31

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.844

Gnomad ASJ AF: 0.857

Gnomad EAS AF: 0.933

Gnomad SAS AF: 0.861

Gnomad FIN AF: 0.851

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.821

Gnomad OTH AF: 0.812

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

GnomAD4 genome AF: 0.808 AC: 122843 AN: 152068 Hom.: 49785 Cov.: 31 AF XY: 0.811 AC XY: 60278 AN XY: 74334

African (AFR) AF: 0.735 AC: 30473 AN: 41442

American (AMR) AF: 0.845 AC: 12904 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.857 AC: 2974 AN: 3472

East Asian (EAS) AF: 0.933 AC: 4824 AN: 5172

South Asian (SAS) AF: 0.861 AC: 4149 AN: 4818

European-Finnish (FIN) AF: 0.851 AC: 8995 AN: 10566

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.821 AC: 55843 AN: 68002

Other (OTH) AF: 0.814 AC: 1719 AN: 2112

Alfa AF: 0.812 Hom.: 13301

Bravo AF: 0.799

Asia WGS AF: 0.897 AC: 3115 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.9
DANN	Benign	0.63
PhyloP100		-0.020
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: rs2033962; hg19: chr2-158638441;