chr2-157737484-G-A
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4BP6_ModerateBS1BS2
The NM_001111067.4(ACVR1):c.*47C>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 0.000542 in 1,609,702 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00037 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00056 ( 12 hom. )
Consequence
ACVR1
NM_001111067.4 3_prime_UTR
NM_001111067.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.50
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.16).
BP6
Variant 2-157737484-G-A is Benign according to our data. Variant chr2-157737484-G-A is described in ClinVar as [Benign]. Clinvar id is 331686.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.000561 (817/1457414) while in subpopulation EAS AF= 0.0202 (798/39500). AF 95% confidence interval is 0.019. There are 12 homozygotes in gnomad4_exome. There are 390 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.
BS2
High AC in GnomAd4 at 56 AD gene.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|---|---|---|---|---|---|---|
| ACVR1 | NM_001111067.4 | c.*47C>T | 3_prime_UTR_variant | 11/11 | ENST00000434821.7 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ACVR1 | ENST00000434821.7 | c.*47C>T | 3_prime_UTR_variant | 11/11 | 1 | NM_001111067.4 | P4 |
Frequencies
GnomAD3 genomes 0.000368 AC: 56AN: 152170Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000610 AC: 150AN: 246070Hom.: 0 AF XY: 0.000518 AC XY: 69AN XY: 133100
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GnomAD4 exome AF: 0.000561 AC: 817AN: 1457414Hom.: 12 Cov.: 30 AF XY: 0.000538 AC XY: 390AN XY: 724968
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GnomAD4 genome 0.000368 AC: 56AN: 152288Hom.: 1 Cov.: 32 AF XY: 0.000403 AC XY: 30AN XY: 74466
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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
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at