chr2-157849312-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001111067.4(ACVR1):​c.-183+26484A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0895 in 152,288 control chromosomes in the GnomAD database, including 719 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 0.089 ( 719 hom., cov: 32)

Consequence

ACVR1
NM_001111067.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.175

Publications

6 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ACVR1NM_001111067.4 linkc.-183+26484A>G intron_variant Intron 1 of 10 ENST00000434821.7 NP_001104537.1 Q04771D3DPA4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ACVR1ENST00000434821.7 linkc.-183+26484A>G intron_variant Intron 1 of 10 1 NM_001111067.4 ENSP00000405004.1 Q04771

Frequencies

GnomAD3 genomes
AF:
0.0894
AC:
13611
AN:
152170
Hom.:
717
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.143
Gnomad AMI
AF:
0.103
Gnomad AMR
AF:
0.0678
Gnomad ASJ
AF:
0.0435
Gnomad EAS
AF:
0.00288
Gnomad SAS
AF:
0.0977
Gnomad FIN
AF:
0.0367
Gnomad MID
AF:
0.0918
Gnomad NFE
AF:
0.0780
Gnomad OTH
AF:
0.0856
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0895
AC:
13627
AN:
152288
Hom.:
719
Cov.:
32
AF XY:
0.0855
AC XY:
6365
AN XY:
74484
show subpopulations
African (AFR)
AF:
0.143
AC:
5956
AN:
41538
American (AMR)
AF:
0.0676
AC:
1035
AN:
15304
Ashkenazi Jewish (ASJ)
AF:
0.0435
AC:
151
AN:
3472
East Asian (EAS)
AF:
0.00289
AC:
15
AN:
5192
South Asian (SAS)
AF:
0.0980
AC:
473
AN:
4826
European-Finnish (FIN)
AF:
0.0367
AC:
390
AN:
10622
Middle Eastern (MID)
AF:
0.102
AC:
30
AN:
294
European-Non Finnish (NFE)
AF:
0.0780
AC:
5305
AN:
68016
Other (OTH)
AF:
0.0843
AC:
178
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
626
1252
1879
2505
3131
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
160
320
480
640
800
<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:
0.0833
Hom.:
98
Bravo
AF:
0.0938
Asia WGS
AF:
0.0490
AC:
172
AN:
3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
8.7
DANN
Benign
0.79
PhyloP100
-0.17
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

Publications

Other links and lift over

dbSNP: rs920522; hg19: chr2-158705824; API