rs503327

Variant names:

• chr3-38482872-C-T
• rs503327
• NM_001106.4:c.1345-266C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001106.4(ACVR2B):​c.1345-266C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0688 in 152,212 control chromosomes in the GnomAD database, including 445 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.069 (445 hom., cov: 31)
• Consequence: ACVR2B NM_001106.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.66
• Publications: 5 publications found

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]

ACVR2B Gene-Disease associations (from GenCC):

• heterotaxy, visceral, 4, autosomal

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 3-38482872-C-T is Benign according to our data. Variant chr3-38482872-C-T is described in ClinVar as Benign. ClinVar VariationId is 1276021.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACVR2B	NM_001106.4	c.1345-266C>T		intron_variant	Intron 10 of 10	ENST00000352511.5	NP_001097.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACVR2B	ENST00000352511.5	c.1345-266C>T		intron_variant	Intron 10 of 10	1	NM_001106.4	ENSP00000340361.3
ACVR2B	ENST00000461232.1	n.5134-266C>T		intron_variant	Intron 9 of 9	1
ACVR2B	ENST00000465020.5	n.1431-266C>T		intron_variant	Intron 9 of 9	2

Frequencies

GnomAD3 genomes AF: 0.0689 AC: 10481 AN: 152094 Hom.: 445 Cov.: 31

Gnomad AFR AF: 0.0173

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.0695

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0375

Gnomad FIN AF: 0.0609

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0808

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0688 AC: 10478 AN: 152212 Hom.: 445 Cov.: 31 AF XY: 0.0666 AC XY: 4955 AN XY: 74412

African (AFR) AF: 0.0172 AC: 716 AN: 41560

American (AMR) AF: 0.0694 AC: 1061 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 486 AN: 3470

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5172

South Asian (SAS) AF: 0.0376 AC: 181 AN: 4818

European-Finnish (FIN) AF: 0.0609 AC: 645 AN: 10598

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7147 AN: 67986

Other (OTH) AF: 0.0799 AC: 169 AN: 2114

Alfa AF: 0.0954 Hom.: 1294

Bravo AF: 0.0659

Asia WGS AF: 0.0190 AC: 70 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.44
DANN	Benign	0.27
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs503327; hg19: chr3-38524363;