Variant chr2-157736740-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBA1

The NM_001111067.4(ACVR1):c.*791A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00973 in 343,062 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.018 ( 76 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 11 hom. )

Consequence

ACVR1
NM_001111067.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.989

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 2-157736740-T-A is Benign according to our data. Variant chr2-157736740-T-A is described in ClinVar as [Benign]. Clinvar id is 331673.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACVR1	NM_001111067.4 linkuse as main transcript	c.*791A>T		3_prime_UTR_variant	11/11	ENST00000434821.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACVR1	ENST00000434821.7 linkuse as main transcript	c.*791A>T		3_prime_UTR_variant	11/11	1	NM_001111067.4	P4

Frequencies

GnomAD3 genomes

AF:

0.0184

AC:

2807

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0608

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00877

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.0150

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.0167

GnomAD4 exome

AF:

0.00275

AC:

524

AN:

190744

Hom.:

Cov.:

AF XY:

0.00236

AC XY:

219

AN XY:

92682

show subpopulations

Gnomad4 AFR exome

AF:

0.0482

Gnomad4 AMR exome

AF:

0.00397

Gnomad4 ASJ exome

AF:

0.00115

Gnomad4 EAS exome

AF:

0.00254

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000269

Gnomad4 OTH exome

AF:

0.00760

GnomAD4 genome

AF:

0.0185

AC:

2814

AN:

152318

Hom.:

Cov.:

AF XY:

0.0181

AC XY:

1349

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0608

Gnomad4 AMR

AF:

0.00876

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.0148

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000412

Gnomad4 OTH

AF:

0.0170

Alfa

AF:

0.0135

Hom.:

Bravo

AF:

0.0200

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Progressive myositis ossificans

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.85

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