2-157770468-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001111067.4(ACVR1):c.690G>A(p.Glu230Glu) 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
NM_001111067.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.982

Publications

33 publications found

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 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

ACVR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 257466.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
ACVR1	NM_001111067.4 link	c.690G>A	p.Glu230Glu	synonymous_variant	Exon 7 of 11	ENST00000434821.7	NP_001104537.1	Q04771D3DPA4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACVR1	ENST00000434821.7 link	c.690G>A	p.Glu230Glu	synonymous_variant	Exon 7 of 11	1	NM_001111067.4	ENSP00000405004.1		Q04771

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

GnomAD2 exomes

AF:

0.969

AC:

243325

AN:

251128

AF XY:

0.973

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 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

African (AFR)

AF:

0.757

AC:

25359

AN:

33480

American (AMR)

AF:

0.982

AC:

43909

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.981

AC:

25646

AN:

26134

East Asian (EAS)

AF:

0.962

AC:

38188

AN:

39696

South Asian (SAS)

AF:

0.972

AC:

83817

AN:

86258

European-Finnish (FIN)

AF:

0.983

AC:

52522

AN:

53416

Middle Eastern (MID)

AF:

0.945

AC:

5449

AN:

5766

European-Non Finnish (NFE)

AF:

0.991

AC:

1102337

AN:

1111946

Other (OTH)

AF:

0.969

AC:

58532

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

1345

2690

4034

5379

6724

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21650

43300

64950

86600

108250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.921

AC:

140184

AN:

152130

Hom.:

65364

Cov.:

AF XY:

0.924

AC XY:

68678

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.759

AC:

31424

AN:

41426

American (AMR)

AF:

0.963

AC:

14734

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.979

AC:

3392

AN:

3466

East Asian (EAS)

AF:

0.969

AC:

5010

AN:

5172

South Asian (SAS)

AF:

0.973

AC:

4692

AN:

4820

European-Finnish (FIN)

AF:

0.986

AC:

10460

AN:

10610

Middle Eastern (MID)

AF:

0.949

AC:

279

AN:

294

European-Non Finnish (NFE)

AF:

0.990

AC:

67323

AN:

68024

Other (OTH)

AF:

0.931

AC:

1964

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

473

946

1418

1891

2364

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

902

1804

2706

3608

4510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.963

Hom.:

116845

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 06, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Progressive myositis ossificans

Benign:2

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

6.1

(source)

DANN

Benign

0.43

PhyloP100

0.98

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over