rs2268753

Positions:

• chr3-38458698-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001106.4(ACVR2B):​c.52+4324C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 151,896 control chromosomes in the GnomAD database, including 15,903 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 0.42 (15903 hom., cov: 31)
• Consequence: ACVR2B NM_001106.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.470

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACVR2B	NM_001106.4	c.52+4324C>T		intron_variant		ENST00000352511.5
ACVR2B	XM_017007515.3	c.70+4014C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACVR2B	ENST00000352511.5	c.52+4324C>T		intron_variant		1	NM_001106.4	P1
ACVR2B	ENST00000465020.5	n.56+4324C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64360 AN: 151778 Hom.: 15905 Cov.: 31

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.444

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

GnomAD4 genome AF: 0.424 AC: 64361 AN: 151896 Hom.: 15903 Cov.: 31 AF XY: 0.421 AC XY: 31232 AN XY: 74236

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.268

Gnomad4 SAS AF: 0.506

Gnomad4 FIN AF: 0.525

Gnomad4 NFE AF: 0.567

Gnomad4 OTH AF: 0.444

Alfa AF: 0.480 Hom.: 2808

Bravo AF: 0.398

Asia WGS AF: 0.399 AC: 1387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.66

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: rs2268753; hg19: chr3-38500189;