3-38487046-G-T

Variant names:

• chr3-38487046-G-T
• rs928813
• NM_001106.4:c.*3714G>T

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.*3714G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 152,376 control chromosomes in the GnomAD database, including 16,228 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (16184 hom., cov: 32)
  • Exomes 𝑓: 0.53 (44 hom.)
• Consequence: ACVR2B NM_001106.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.19
• Publications: 10 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 3-38487046-G-T is Benign according to our data. Variant chr3-38487046-G-T is described in ClinVar as Benign. ClinVar VariationId is 344981.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.*3714G>T		3_prime_UTR	Exon 11 of 11	NP_001097.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACVR2B	ENST00000352511.5	TSL:1 MANE Select	c.*3714G>T		3_prime_UTR	Exon 11 of 11	ENSP00000340361.3

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64830 AN: 151930 Hom.: 16186 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.448

GnomAD4 exome AF: 0.527 AC: 174 AN: 330 Hom.: 44 Cov.: 0 AF XY: 0.516 AC XY: 128 AN XY: 248

African (AFR) AF: 0.250 AC: 3 AN: 12

American (AMR) AF: 0.167 AC: 2 AN: 12

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 3 AN: 6

East Asian (EAS) AF: 0.200 AC: 2 AN: 10

South Asian (SAS) AF: 0.750 AC: 3 AN: 4

European-Finnish (FIN) AF: 0.300 AC: 3 AN: 10

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.580 AC: 153 AN: 264

Other (OTH) AF: 0.500 AC: 5 AN: 10

GnomAD4 genome AF: 0.426 AC: 64830 AN: 152046 Hom.: 16184 Cov.: 32 AF XY: 0.424 AC XY: 31481 AN XY: 74298

African (AFR) AF: 0.177 AC: 7360 AN: 41522

American (AMR) AF: 0.387 AC: 5910 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1709 AN: 3468

East Asian (EAS) AF: 0.268 AC: 1381 AN: 5148

South Asian (SAS) AF: 0.509 AC: 2451 AN: 4812

European-Finnish (FIN) AF: 0.531 AC: 5604 AN: 10558

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

European-Non Finnish (NFE) AF: 0.573 AC: 38903 AN: 67946

Other (OTH) AF: 0.448 AC: 947 AN: 2114

Alfa AF: 0.486 Hom.: 7754

Bravo AF: 0.400

Asia WGS AF: 0.401 AC: 1392 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.94
CADD	Benign	0.15
DANN	Benign	0.67
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs928813; hg19: chr3-38528537;