rs1046048

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001106.4(ACVR2B):c.1458C>T(p.Asn486Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 1,613,586 control chromosomes in the GnomAD database, including 232,022 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 16163 hom., cov: 30)

Exomes 𝑓: 0.54 ( 215859 hom. )

Consequence

ACVR2B
NM_001106.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 2.06

Publications

29 publications found

Variant links:

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)

ACVR2B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 3-38483251-C-T is Benign according to our data. Variant chr3-38483251-C-T is described in ClinVar as Benign. ClinVar VariationId is 257467.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.06 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACVR2B	NM_001106.4	MANE Select	c.1458C>T	p.Asn486Asn	synonymous	Exon 11 of 11	NP_001097.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ACVR2B	ENST00000352511.5	TSL:1 MANE Select	c.1458C>T	p.Asn486Asn	synonymous	Exon 11 of 11	ENSP00000340361.3
ACVR2B	ENST00000461232.1	TSL:1	n.5247C>T		non_coding_transcript_exon	Exon 10 of 10
ACVR2B	ENST00000922132.1		c.1434C>T	p.Asn478Asn	synonymous	Exon 11 of 11	ENSP00000592191.1

Frequencies

GnomAD3 genomes

AF:

0.427

AC:

64752

AN:

151688

Hom.:

16164

Cov.:

show subpopulations

Gnomad AFR

AF:

0.178

Gnomad AMI

AF:

0.466

Gnomad AMR

AF:

0.388

Gnomad ASJ

AF:

0.493

Gnomad EAS

AF:

0.268

Gnomad SAS

AF:

0.510

Gnomad FIN

AF:

0.530

Gnomad MID

AF:

0.471

Gnomad NFE

AF:

0.573

Gnomad OTH

AF:

0.447

GnomAD2 exomes

AF:

0.477

AC:

119999

AN:

251464

AF XY:

0.491

show subpopulations

Gnomad AFR exome

AF:

0.175

Gnomad AMR exome

AF:

0.333

Gnomad ASJ exome

AF:

0.499

Gnomad EAS exome

AF:

0.269

Gnomad FIN exome

AF:

0.534

Gnomad NFE exome

AF:

0.573

Gnomad OTH exome

AF:

0.499

GnomAD4 exome

AF:

0.536

AC:

783446

AN:

1461780

Hom.:

215859

Cov.:

AF XY:

0.537

AC XY:

390623

AN XY:

727204

show subpopulations

African (AFR)

AF:

0.161

AC:

5404

AN:

33478

American (AMR)

AF:

0.338

AC:

15126

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.493

AC:

12873

AN:

26136

East Asian (EAS)

AF:

0.305

AC:

12100

AN:

39700

South Asian (SAS)

AF:

0.520

AC:

44864

AN:

86256

European-Finnish (FIN)

AF:

0.541

AC:

28909

AN:

53412

Middle Eastern (MID)

AF:

0.478

AC:

2755

AN:

5768

European-Non Finnish (NFE)

AF:

0.568

AC:

631121

AN:

1111920

Other (OTH)

AF:

0.502

AC:

30294

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

22071

44143

66214

88286

110357

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17208

34416

51624

68832

86040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.427

AC:

64754

AN:

151806

Hom.:

16163

Cov.:

AF XY:

0.424

AC XY:

31420

AN XY:

74146

show subpopulations

African (AFR)

AF:

0.177

AC:

7341

AN:

41416

American (AMR)

AF:

0.387

AC:

5909

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.493

AC:

1708

AN:

3468

East Asian (EAS)

AF:

0.268

AC:

1377

AN:

5136

South Asian (SAS)

AF:

0.510

AC:

2451

AN:

4806

European-Finnish (FIN)

AF:

0.530

AC:

5565

AN:

10492

Middle Eastern (MID)

AF:

0.473

AC:

138

AN:

292

European-Non Finnish (NFE)

AF:

0.573

AC:

38902

AN:

67932

Other (OTH)

AF:

0.447

AC:

939

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1610

3219

4829

6438

8048

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

600

1200

1800

2400

3000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.510

Hom.:

61328

Bravo

AF:

0.400

Asia WGS

AF:

0.401

AC:

1392

AN:

3478

EpiCase

AF:

0.554

EpiControl

AF:

0.562

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Heterotaxy, visceral, 4, autosomal (5)

not specified (4)

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

9.1

(source)

DANN

Benign

0.74

PhyloP100

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over