3-38487046-G-T

Variant names:

• chr3-38487046-G-T
• rs928813
• NM_001106.4:c.*3714G>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001106.4(ACVR2B):​c.*3714G>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 0.427 in 152,376 control chromosomes in the GnomAD database, including 16,228 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (16184 hom., cov: 32)
  • Exomes 𝑓: 0.53 (44 hom.)
• Consequence: ACVR2B NM_001106.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.19

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 3-38487046-G-T is Benign according to our data. Variant chr3-38487046-G-T is described in ClinVar as [Benign]. Clinvar id is 344981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACVR2B	NM_001106.4	c.*3714G>T		3_prime_UTR_variant	Exon 11 of 11	ENST00000352511.5	NP_001097.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACVR2B	ENST00000352511.5	c.*3714G>T		3_prime_UTR_variant	Exon 11 of 11	1	NM_001106.4	ENSP00000340361.3

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64830 AN: 151930 Hom.: 16186 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.448

GnomAD4 exome AF: 0.527 AC: 174 AN: 330 Hom.: 44 Cov.: 0 AF XY: 0.516 AC XY: 128 AN XY: 248

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.200

Gnomad4 SAS exome AF: 0.750

Gnomad4 FIN exome AF: 0.300

Gnomad4 NFE exome AF: 0.580

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.426 AC: 64830 AN: 152046 Hom.: 16184 Cov.: 32 AF XY: 0.424 AC XY: 31481 AN XY: 74298

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.387

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.268

Gnomad4 SAS AF: 0.509

Gnomad4 FIN AF: 0.531

Gnomad4 NFE AF: 0.573

Gnomad4 OTH AF: 0.448

Alfa AF: 0.493 Hom.: 6354

Bravo AF: 0.400

Asia WGS AF: 0.401 AC: 1392 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Heterotaxy, visceral, 4, autosomal Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.15
DANN	Benign	0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs928813; hg19: chr3-38528537;