3-38478523-G-A
Variant names:
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_001106.4(ACVR2B):c.666+5G>A variant causes a splice region, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0013 in 1,614,118 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. 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 splice_region, intron
NM_001106.4 splice_region, intron
Scores
2
Splicing: ADA: 0.9992
2
Clinical Significance
Conservation
PhyloP100: 7.48
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 -16 ACMG points.
BP6
Variant 3-38478523-G-A is Benign according to our data. Variant chr3-38478523-G-A is described in ClinVar as [Benign]. Clinvar id is 238305.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-38478523-G-A is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.007 (1066/152302) while in subpopulation AFR AF= 0.0247 (1026/41564). AF 95% confidence interval is 0.0234. There are 8 homozygotes in gnomad4. There are 494 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1066 AD gene.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ACVR2B | ENST00000352511.5 | c.666+5G>A | splice_region_variant, intron_variant | Intron 5 of 10 | 1 | NM_001106.4 | ENSP00000340361.3 | |||
ACVR2B | ENST00000461232.1 | n.4455+5G>A | splice_region_variant, intron_variant | Intron 4 of 9 | 1 | |||||
ACVR2B | ENST00000465020.5 | n.752+5G>A | splice_region_variant, intron_variant | Intron 4 of 9 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00699 AC: 1064AN: 152184Hom.: 9 Cov.: 32
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GnomAD3 exomes AF: 0.00180 AC: 452AN: 251260Hom.: 6 AF XY: 0.00121 AC XY: 164AN XY: 135814
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GnomAD4 exome AF: 0.000705 AC: 1031AN: 1461816Hom.: 13 Cov.: 33 AF XY: 0.000550 AC XY: 400AN XY: 727208
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GnomAD4 genome AF: 0.00700 AC: 1066AN: 152302Hom.: 8 Cov.: 32 AF XY: 0.00663 AC XY: 494AN XY: 74470
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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 | Labcorp Genetics (formerly Invitae), Labcorp | Jan 30, 2025 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Uncertain
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
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dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at