rs16842009
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The NM_001111067.4(ACVR1):c.1396-93G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00222 in 1,515,496 control chromosomes in the GnomAD database, including 76 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 0.012 ( 48 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 28 hom. )
Consequence
ACVR1
NM_001111067.4 intron
NM_001111067.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.861
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 -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0121 (1843/152220) while in subpopulation AFR AF= 0.0419 (1741/41526). AF 95% confidence interval is 0.0403. There are 48 homozygotes in gnomad4. There are 856 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 1843 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACVR1 | NM_001111067.4 | c.1396-93G>A | intron_variant | ENST00000434821.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACVR1 | ENST00000434821.7 | c.1396-93G>A | intron_variant | 1 | NM_001111067.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0121 AC: 1845AN: 152102Hom.: 48 Cov.: 32
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GnomAD4 exome AF: 0.00111 AC: 1515AN: 1363276Hom.: 28 AF XY: 0.000924 AC XY: 632AN XY: 684046
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GnomAD4 genome ? AF: 0.0121 AC: 1843AN: 152220Hom.: 48 Cov.: 32 AF XY: 0.0115 AC XY: 856AN XY: 74430
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ClinVar
Not reported inComputational scores
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Name
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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