dbSNP rs34050429: ACVR1B:c.1261+172G>A (chr12-51987114-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004302.5(ACVR1B):c.1261+172G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00922 in 867,400 control chromosomes in the GnomAD database, including 458 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.034 ( 297 hom., cov: 33)

Exomes 𝑓: 0.0040 ( 161 hom. )

Consequence

ACVR1B
NM_004302.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.519

Publications

2 publications found

Variant links:

Genes affected

ACVR1B (HGNC:172): (activin A receptor type 1B) This gene encodes an activin A type IB receptor. 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 and two type II receptors. This protein is a type I receptor which is essential for signaling. Mutations in this gene are associated with pituitary tumors. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Jun 2010]

ACVR1B Gene-Disease associations (from GenCC):

malignant pancreatic neoplasm
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Ambry Genetics

ACVR1B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019359291).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACVR1B	NM_004302.5 link	c.1261+172G>A		intron_variant	Intron 7 of 8	ENST00000257963.9	NP_004293.1	P36896-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACVR1B	ENST00000257963.9 link	c.1261+172G>A		intron_variant	Intron 7 of 8	1	NM_004302.5	ENSP00000257963.4		P36896-1

Frequencies

GnomAD3 genomes

AF:

0.0340

AC:

5167

AN:

152120

Hom.:

298

Cov.:

show subpopulations

Gnomad AFR

AF:

0.119

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0115

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.0273

GnomAD2 exomes

AF:

0.00853

AC:

1441

AN:

168866

AF XY:

0.00619

show subpopulations

Gnomad AFR exome

AF:

0.133

Gnomad AMR exome

AF:

0.00408

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000304

Gnomad NFE exome

AF:

0.000269

Gnomad OTH exome

AF:

0.00491

GnomAD4 exome

AF:

0.00396

AC:

2832

AN:

715162

Hom.:

161

Cov.:

AF XY:

0.00307

AC XY:

1161

AN XY:

378510

show subpopulations

African (AFR)

AF:

0.120

AC:

2226

AN:

18574

American (AMR)

AF:

0.00532

AC:

190

AN:

35726

Ashkenazi Jewish (ASJ)

AF:

0.0000953

AC:

AN:

20978

East Asian (EAS)

AF:

0.0000296

AC:

AN:

33744

South Asian (SAS)

AF:

0.000281

AC:

AN:

67612

European-Finnish (FIN)

AF:

0.000179

AC:

AN:

50250

Middle Eastern (MID)

AF:

0.00387

AC:

AN:

4390

European-Non Finnish (NFE)

AF:

0.000185

AC:

AN:

448300

Other (OTH)

AF:

0.00801

AC:

285

AN:

35588

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

161

322

482

643

804

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

152

190

<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:

0.0339

AC:

5167

AN:

152238

Hom.:

297

Cov.:

AF XY:

0.0327

AC XY:

2431

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.118

AC:

4914

AN:

41506

American (AMR)

AF:

0.0115

AC:

176

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000250

AC:

AN:

68014

Other (OTH)

AF:

0.0270

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

227

454

681

908

1135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<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:

0.0288

Hom.:

203

Bravo

AF:

0.0384

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.124

AC:

328

ESP6500EA

AF:

0.000218

AC:

ExAC

AF:

0.00918

AC:

1044

Asia WGS

AF:

0.00635

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.38

CADD

Benign

7.2

(source)

DANN

Benign

0.77

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.31

MetaRNN

Benign

0.0019

MetaSVM

Benign

-1.1

PhyloP100

0.52

PROVEAN

Benign

-0.79

REVEL

Benign

0.035

Sift

Pathogenic

0.0

Polyphen

0.057

Vest4

0.11

MVP

0.58

ClinPred

0.031

GERP RS

0.36

Mutation Taster

=94/6

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over