NM_001106.4:c.53-5999G>A

Variant names:

• chr3-38471288-G-A
• rs2276541
• NM_001106.4:c.53-5999G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001106.4(ACVR2B):​c.53-5999G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 152,088 control chromosomes in the GnomAD database, including 19,989 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.49 (19989 hom., cov: 33)
• Consequence: ACVR2B NM_001106.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365
• Publications: 9 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACVR2B	NM_001106.4	c.53-5999G>A		intron_variant	Intron 1 of 10	ENST00000352511.5	NP_001097.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACVR2B	ENST00000352511.5	c.53-5999G>A		intron_variant	Intron 1 of 10	1	NM_001106.4	ENSP00000340361.3
ACVR2B	ENST00000465020.5	n.57-5999G>A		intron_variant	Intron 1 of 9	2

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73754 AN: 151970 Hom.: 19992 Cov.: 33

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.498

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

GnomAD4 genome AF: 0.485 AC: 73780 AN: 152088 Hom.: 19989 Cov.: 33 AF XY: 0.484 AC XY: 36023 AN XY: 74352

African (AFR) AF: 0.232 AC: 9624 AN: 41482

American (AMR) AF: 0.527 AC: 8058 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 1903 AN: 3472

East Asian (EAS) AF: 0.462 AC: 2385 AN: 5166

South Asian (SAS) AF: 0.570 AC: 2745 AN: 4814

European-Finnish (FIN) AF: 0.549 AC: 5802 AN: 10568

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.612 AC: 41628 AN: 67980

Other (OTH) AF: 0.496 AC: 1048 AN: 2112

Alfa AF: 0.531 Hom.: 3030

Bravo AF: 0.467

Asia WGS AF: 0.516 AC: 1792 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.69
DANN	Benign	0.16
PhyloP100		0.36
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: rs2276541; hg19: chr3-38512779;