chr3-38477353-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001106.4(ACVR2B):c.119G>A(p.Arg40His) variant causes a missense change. The variant allele was found at a frequency of 0.000846 in 1,614,162 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0036 ( 8 hom., cov: 32)

Exomes 𝑓: 0.00056 ( 5 hom. )

Consequence

ACVR2B
NM_001106.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1B:6

Conservation

PhyloP100: 4.49

Publications

13 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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009315461).

BP6

Variant 3-38477353-G-A is Benign according to our data. Variant chr3-38477353-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 6858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 554 AD gene.

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.119G>A	p.Arg40His	missense	Exon 2 of 11	NP_001097.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ACVR2B	ENST00000352511.5	TSL:1 MANE Select	c.119G>A	p.Arg40His	missense	Exon 2 of 11	ENSP00000340361.3
ACVR2B	ENST00000461232.1	TSL:1	n.3908G>A		non_coding_transcript_exon	Exon 1 of 10
ACVR2B	ENST00000465020.5	TSL:2	n.123G>A		non_coding_transcript_exon	Exon 2 of 10

Frequencies

GnomAD3 genomes

AF:

0.00363

AC:

553

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00111

AC:

279

AN:

251194

AF XY:

0.000840

show subpopulations

Gnomad AFR exome

AF:

0.0144

Gnomad AMR exome

AF:

0.000492

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000185

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.000555

AC:

812

AN:

1461846

Hom.:

Cov.:

AF XY:

0.000507

AC XY:

369

AN XY:

727226

show subpopulations

African (AFR)

AF:

0.0138

AC:

462

AN:

33480

American (AMR)

AF:

0.000671

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0000562

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00208

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000204

AC:

227

AN:

1111986

Other (OTH)

AF:

0.00123

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

108

162

216

270

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<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:

0.00364

AC:

554

AN:

152316

Hom.:

Cov.:

AF XY:

0.00342

AC XY:

255

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0121

AC:

501

AN:

41558

American (AMR)

AF:

0.00196

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

68026

Other (OTH)

AF:

0.00331

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

122

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00149

Hom.:

Bravo

AF:

0.00454

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.0136

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00137

AC:

166

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000237

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Heterotaxy, visceral, 4, autosomal (5)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Uncertain

-0.030

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.65

Eigen

Benign

0.013

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.88

MetaRNN

Benign

0.0093

MetaSVM

Uncertain

0.51

MutationAssessor

Benign

1.7

PhyloP100

4.5

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.2

REVEL

Uncertain

0.44

Sift

Benign

0.045

Sift4G

Benign

0.12

Polyphen

0.056

Vest4

0.20

MVP

0.87

MPC

1.2

ClinPred

0.031

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.56

Mutation Taster

=91/9

polymorphism

(source)

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

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over