rs1058945

Variant names:

• chr3-38491020-G-A
• rs1058945
• NM_001106.4:c.*7688G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001106.4(ACVR2B):​c.*7688G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 152,208 control chromosomes in the GnomAD database, including 16,258 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (16199 hom., cov: 32)
  • Exomes 𝑓: 0.51 (59 hom.)
• Consequence: ACVR2B NM_001106.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0220
• Publications: 19 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 3-38491020-G-A is Benign according to our data. Variant chr3-38491020-G-A is described in ClinVar as Benign. ClinVar VariationId is 345025.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.

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.*7688G>A		3_prime_UTR	Exon 11 of 11	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.*7688G>A		3_prime_UTR	Exon 11 of 11	ENSP00000340361.3	Q13705-1

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64856 AN: 151662 Hom.: 16200 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.449

GnomAD4 exome AF: 0.509 AC: 218 AN: 428 Hom.: 59 Cov.: 0 AF XY: 0.523 AC XY: 134 AN XY: 256

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.512 AC: 216 AN: 422

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.427 AC: 64858 AN: 151780 Hom.: 16199 Cov.: 32 AF XY: 0.425 AC XY: 31509 AN XY: 74170

African (AFR) AF: 0.178 AC: 7366 AN: 41308

American (AMR) AF: 0.387 AC: 5916 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1711 AN: 3470

East Asian (EAS) AF: 0.269 AC: 1388 AN: 5152

South Asian (SAS) AF: 0.510 AC: 2454 AN: 4808

European-Finnish (FIN) AF: 0.533 AC: 5603 AN: 10512

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.573 AC: 38910 AN: 67952

Other (OTH) AF: 0.449 AC: 947 AN: 2108

Alfa AF: 0.509 Hom.: 27456

Bravo AF: 0.400

Asia WGS AF: 0.401 AC: 1393 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Heterotaxy, visceral, 4, autosomal (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	3.1
DANN	Benign	0.77
PhyloP100		-0.022
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: rs1058945; hg19: chr3-38532511;