chr3-38454302-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001106.4(ACVR2B):c.-21C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000766 in 1,266,972 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000099 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000073 ( 1 hom. )
Consequence
ACVR2B
NM_001106.4 5_prime_UTR
NM_001106.4 5_prime_UTR
Scores
1
1
Clinical Significance
Conservation
PhyloP100: 2.07
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 Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.24).
BS2
?
High AC in GnomAd at 15 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACVR2B | NM_001106.4 | c.-21C>T | 5_prime_UTR_variant | 1/11 | ENST00000352511.5 | ||
ACVR2B-AS1 | NR_028389.1 | n.318+201G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACVR2B | ENST00000352511.5 | c.-21C>T | 5_prime_UTR_variant | 1/11 | 1 | NM_001106.4 | P1 | ||
ACVR2B-AS1 | ENST00000441531.1 | n.318+201G>A | intron_variant, non_coding_transcript_variant | 2 | |||||
ACVR2B | ENST00000465020.5 | upstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000993 AC: 15AN: 151102Hom.: 0 Cov.: 31
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GnomAD4 exome AF: 0.0000735 AC: 82AN: 1115762Hom.: 1 Cov.: 30 AF XY: 0.0000967 AC XY: 52AN XY: 537758
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Heterotaxy, visceral, 4, autosomal Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
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