2-157770468-C-T

Position:

chr2-157770468-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The ENST00000434821.7(ACVR1):c.690G>A(p.Glu230=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.976 in 1,613,942 control chromosomes in the GnomAD database, including 771,475 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.92 ( 65364 hom., cov: 30)

Exomes 𝑓: 0.98 ( 706111 hom. )

Consequence

ACVR1
ENST00000434821.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.982

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 2-157770468-C-T is Benign according to our data. Variant chr2-157770468-C-T is described in ClinVar as [Benign]. Clinvar id is 257466.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-157770468-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.982 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.983 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACVR1	NM_001111067.4 linkuse as main transcript	c.690G>A	p.Glu230=	synonymous_variant	7/11	ENST00000434821.7	NP_001104537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACVR1	ENST00000434821.7 linkuse as main transcript	c.690G>A	p.Glu230=	synonymous_variant	7/11	1	NM_001111067.4	ENSP00000405004	P4

Frequencies

GnomAD3 genomes

AF:

0.922

AC:

140095

AN:

152012

Hom.:

65329

Cov.:

show subpopulations

Gnomad AFR

AF:

0.759

Gnomad AMI

AF:

0.993

Gnomad AMR

AF:

0.963

Gnomad ASJ

AF:

0.979

Gnomad EAS

AF:

0.969

Gnomad SAS

AF:

0.973

Gnomad FIN

AF:

0.986

Gnomad MID

AF:

0.949

Gnomad NFE

AF:

0.990

Gnomad OTH

AF:

0.931

GnomAD3 exomes

AF:

0.969

AC:

243325

AN:

251128

Hom.:

118292

AF XY:

0.973

AC XY:

131992

AN XY:

135720

show subpopulations

Gnomad AFR exome

AF:

0.756

Gnomad AMR exome

AF:

0.984

Gnomad ASJ exome

AF:

0.982

Gnomad EAS exome

AF:

0.972

Gnomad SAS exome

AF:

0.973

Gnomad FIN exome

AF:

0.985

Gnomad NFE exome

AF:

0.989

Gnomad OTH exome

AF:

0.973

GnomAD4 exome

AF:

0.982

AC:

1435759

AN:

1461812

Hom.:

706111

Cov.:

AF XY:

0.983

AC XY:

714540

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.757

Gnomad4 AMR exome

AF:

0.982

Gnomad4 ASJ exome

AF:

0.981

Gnomad4 EAS exome

AF:

0.962

Gnomad4 SAS exome

AF:

0.972

Gnomad4 FIN exome

AF:

0.983

Gnomad4 NFE exome

AF:

0.991

Gnomad4 OTH exome

AF:

0.969

GnomAD4 genome

AF:

0.921

AC:

140184

AN:

152130

Hom.:

65364

Cov.:

AF XY:

0.924

AC XY:

68678

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.759

Gnomad4 AMR

AF:

0.963

Gnomad4 ASJ

AF:

0.979

Gnomad4 EAS

AF:

0.969

Gnomad4 SAS

AF:

0.973

Gnomad4 FIN

AF:

0.986

Gnomad4 NFE

AF:

0.990

Gnomad4 OTH

AF:

0.931

Alfa

AF:

0.971

Hom.:

87519

Bravo

AF:

0.913

Asia WGS

AF:

0.952

AC:

3313

AN:

3478

EpiCase

AF:

0.990

EpiControl

AF:

0.988

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 06, 2020	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Progressive myositis ossificans

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

6.1

DANN

Benign

0.43

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over