rs7374458

Variant names:

• chr3-38489720-T-G
• rs7374458
• NM_001106.4:c.*6388T>G

Your query was ambiguous. Multiple possible variants found:

• chr3-38489720-T-G
• chr3-38489720-T-A
• chr3-38489720-T-C

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.*6388T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 152,442 control chromosomes in the GnomAD database, including 20,317 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (20262 hom., cov: 32)
  • Exomes 𝑓: 0.54 (55 hom.)
• Consequence: ACVR2B NM_001106.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.284
• Publications: 13 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=-0.92).
• BP6: Variant 3-38489720-T-G is Benign according to our data. Variant chr3-38489720-T-G is described in ClinVar as Benign. ClinVar VariationId is 345010.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.613 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.*6388T>G		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.*6388T>G		3_prime_UTR	Exon 11 of 11	ENSP00000340361.3	Q13705-1

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74181 AN: 151920 Hom.: 20261 Cov.: 32

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.618

Gnomad OTH AF: 0.501

GnomAD4 exome AF: 0.540 AC: 218 AN: 404 Hom.: 55 Cov.: 0 AF XY: 0.561 AC XY: 137 AN XY: 244

African (AFR) AF: 0.500 AC: 1 AN: 2

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: 0.541 AC: 211 AN: 390

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.667 AC: 4 AN: 6

Other (OTH) AF: 0.333 AC: 2 AN: 6

GnomAD4 genome AF: 0.488 AC: 74214 AN: 152038 Hom.: 20262 Cov.: 32 AF XY: 0.488 AC XY: 36230 AN XY: 74314

African (AFR) AF: 0.231 AC: 9591 AN: 41476

American (AMR) AF: 0.530 AC: 8096 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 1919 AN: 3468

East Asian (EAS) AF: 0.461 AC: 2390 AN: 5182

South Asian (SAS) AF: 0.573 AC: 2759 AN: 4812

European-Finnish (FIN) AF: 0.554 AC: 5840 AN: 10542

Middle Eastern (MID) AF: 0.497 AC: 145 AN: 292

European-Non Finnish (NFE) AF: 0.618 AC: 41982 AN: 67968

Other (OTH) AF: 0.500 AC: 1052 AN: 2104

Alfa AF: 0.582 Hom.: 37748

Bravo AF: 0.470

Asia WGS AF: 0.518 AC: 1799 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	-0.92
CADD	Benign	3.8
DANN	Benign	0.64
PhyloP100		-0.28
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: rs7374458; hg19: chr3-38531211;