rs2228012
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001106.4(ACVR2B):c.993C>T(p.Ser331=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0013 in 1,614,134 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0070 ( 8 hom., cov: 32)
Exomes 𝑓: 0.00071 ( 13 hom. )
Consequence
ACVR2B
NM_001106.4 synonymous
NM_001106.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.651
Genes affected
ACVR2B (HGNC:174): (activin A receptor type 2B) 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. Type II receptors are considered to be constitutively active kinases. This gene encodes activin A type IIB receptor, which displays a 3- to 4-fold higher affinity for the ligand than activin A type II receptor. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
?
Variant 3-38481384-C-T is Benign according to our data. Variant chr3-38481384-C-T is described in ClinVar as [Benign]. Clinvar id is 238306.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.651 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00701 (1067/152302) while in subpopulation AFR AF= 0.0247 (1027/41564). AF 95% confidence interval is 0.0235. There are 8 homozygotes in gnomad4. There are 496 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 1067 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACVR2B | NM_001106.4 | c.993C>T | p.Ser331= | synonymous_variant | 8/11 | ENST00000352511.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACVR2B | ENST00000352511.5 | c.993C>T | p.Ser331= | synonymous_variant | 8/11 | 1 | NM_001106.4 | P1 | |
ACVR2B | ENST00000461232.1 | n.4782C>T | non_coding_transcript_exon_variant | 7/10 | 1 | ||||
ACVR2B | ENST00000465020.5 | n.1079C>T | non_coding_transcript_exon_variant | 7/10 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00700 AC: 1065AN: 152184Hom.: 9 Cov.: 32
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GnomAD3 exomes AF: 0.00180 AC: 453AN: 251458Hom.: 6 AF XY: 0.00121 AC XY: 165AN XY: 135918
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GnomAD4 exome AF: 0.000711 AC: 1039AN: 1461832Hom.: 13 Cov.: 31 AF XY: 0.000560 AC XY: 407AN XY: 727222
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GnomAD4 genome ? AF: 0.00701 AC: 1067AN: 152302Hom.: 8 Cov.: 32 AF XY: 0.00666 AC XY: 496AN XY: 74482
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Heterotaxy, visceral, 4, autosomal Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at