rs2227861

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001111067.4(ACVR1):c.270C>T(p.Ala90Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 1,613,950 control chromosomes in the GnomAD database, including 465,080 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 34999 hom., cov: 31)

Exomes 𝑓: 0.76 ( 430081 hom. )

Consequence

ACVR1
NM_001111067.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.73

Publications

29 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 2-157780398-G-A is Benign according to our data. Variant chr2-157780398-G-A is described in ClinVar as Benign. ClinVar VariationId is 257464.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.73 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACVR1	NM_001111067.4 link	c.270C>T	p.Ala90Ala	synonymous_variant	Exon 4 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.270C>T	p.Ala90Ala	synonymous_variant	Exon 4 of 11	1	NM_001111067.4	ENSP00000405004.1		Q04771

Frequencies

GnomAD3 genomes

AF:

0.638

AC:

96988

AN:

151972

Hom.:

34987

Cov.:

show subpopulations

Gnomad AFR

AF:

0.271

Gnomad AMI

AF:

0.683

Gnomad AMR

AF:

0.758

Gnomad ASJ

AF:

0.802

Gnomad EAS

AF:

0.923

Gnomad SAS

AF:

0.827

Gnomad FIN

AF:

0.779

Gnomad MID

AF:

0.741

Gnomad NFE

AF:

0.767

Gnomad OTH

AF:

0.664

GnomAD2 exomes

AF:

0.762

AC:

191486

AN:

251244

AF XY:

0.772

show subpopulations

Gnomad AFR exome

AF:

0.256

Gnomad AMR exome

AF:

0.830

Gnomad ASJ exome

AF:

0.806

Gnomad EAS exome

AF:

0.927

Gnomad FIN exome

AF:

0.781

Gnomad NFE exome

AF:

0.762

Gnomad OTH exome

AF:

0.763

GnomAD4 exome

AF:

0.762

AC:

1113826

AN:

1461860

Hom.:

430081

Cov.:

AF XY:

0.765

AC XY:

556230

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.242

AC:

8101

AN:

33480

American (AMR)

AF:

0.818

AC:

36594

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.805

AC:

21041

AN:

26136

East Asian (EAS)

AF:

0.918

AC:

36429

AN:

39700

South Asian (SAS)

AF:

0.827

AC:

71298

AN:

86256

European-Finnish (FIN)

AF:

0.783

AC:

41821

AN:

53420

Middle Eastern (MID)

AF:

0.757

AC:

4364

AN:

5768

European-Non Finnish (NFE)

AF:

0.763

AC:

848748

AN:

1111980

Other (OTH)

AF:

0.752

AC:

45430

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

16266

32532

48797

65063

81329

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20352

40704

61056

81408

101760

<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:

0.638

AC:

97018

AN:

152090

Hom.:

34999

Cov.:

AF XY:

0.645

AC XY:

47978

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.271

AC:

11228

AN:

41426

American (AMR)

AF:

0.758

AC:

11583

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.802

AC:

2782

AN:

3470

East Asian (EAS)

AF:

0.923

AC:

4777

AN:

5176

South Asian (SAS)

AF:

0.827

AC:

3988

AN:

4822

European-Finnish (FIN)

AF:

0.779

AC:

8250

AN:

10592

Middle Eastern (MID)

AF:

0.748

AC:

220

AN:

294

European-Non Finnish (NFE)

AF:

0.767

AC:

52163

AN:

68004

Other (OTH)

AF:

0.666

AC:

1404

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1419

2839

4258

5678

7097

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

762

1524

2286

3048

3810

<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:

0.711

Hom.:

20568

Bravo

AF:

0.614

Asia WGS

AF:

0.836

AC:

2907

AN:

3478

EpiCase

AF:

0.765

EpiControl

AF:

0.764

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Sep 04, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

Progressive myositis ossificans

Benign:2

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 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

-0.66

CADD

Benign

1.1

(source)

DANN

Benign

0.71

PhyloP100

-1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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