3-38482820-A-G

Variant names:

• chr3-38482820-A-G
• rs7373828
• NM_001106.4:c.1344+260A>G

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.1344+260A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 151,858 control chromosomes in the GnomAD database, including 17,408 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.46 (17408 hom., cov: 31)
• Consequence: ACVR2B NM_001106.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0850
• Publications: 8 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, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 3-38482820-A-G is Benign according to our data. Variant chr3-38482820-A-G is described in ClinVar as Benign. ClinVar VariationId is 1249647.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001106.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACVR2B	NM_001106.4	MANE Select	c.1344+260A>G		intron	N/A	NP_001097.2	Q13705-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACVR2B	ENST00000352511.5	TSL:1 MANE Select	c.1344+260A>G		intron	N/A	ENSP00000340361.3	Q13705-1
	ACVR2B	ENST00000461232.1	TSL:1	n.5133+260A>G		intron	N/A
	ACVR2B	ENST00000922132.1		c.1320+260A>G		intron	N/A	ENSP00000592191.1

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69836 AN: 151738 Hom.: 17407 Cov.: 31

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.477

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

GnomAD4 genome AF: 0.460 AC: 69845 AN: 151858 Hom.: 17408 Cov.: 31 AF XY: 0.456 AC XY: 33841 AN XY: 74220

African (AFR) AF: 0.292 AC: 12088 AN: 41414

American (AMR) AF: 0.400 AC: 6103 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 1740 AN: 3468

East Asian (EAS) AF: 0.269 AC: 1383 AN: 5144

South Asian (SAS) AF: 0.510 AC: 2452 AN: 4806

European-Finnish (FIN) AF: 0.531 AC: 5593 AN: 10532

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.573 AC: 38916 AN: 67922

Other (OTH) AF: 0.476 AC: 1006 AN: 2112

Alfa AF: 0.468 Hom.: 3395

Bravo AF: 0.439

Asia WGS AF: 0.406 AC: 1410 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.3
DANN	Benign	0.44
PhyloP100		-0.085
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: rs7373828; hg19: chr3-38524311;