Variant chr12-51987114-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ACVR1B	NM_004302.5 linkuse as main transcript	c.1261+172G>A		intron_variant		ENST00000257963.9	NP_004293.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACVR1B	ENST00000257963.9 linkuse as main transcript	c.1261+172G>A		intron_variant		1	NM_004302.5	ENSP00000257963	P1	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

GnomAD3 exomes

AF:

0.00853

AC:

1441

AN:

168866

Hom.:

AF XY:

0.00619

AC XY:

558

AN XY:

90086

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 SAS exome

AF:

0.000244

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

Gnomad4 AFR exome

AF:

0.120

Gnomad4 AMR exome

AF:

0.00532

Gnomad4 ASJ exome

AF:

0.0000953

Gnomad4 EAS exome

AF:

0.0000296

Gnomad4 SAS exome

AF:

0.000281

Gnomad4 FIN exome

AF:

0.000179

Gnomad4 NFE exome

AF:

0.000185

Gnomad4 OTH exome

AF:

0.00801

GnomAD4 genome

AF:

0.0339

AC:

5167

AN:

152238

Hom.:

297

Cov.:

AF XY:

0.0327

AC XY:

2431

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.118

Gnomad4 AMR

AF:

0.0115

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.0270

Alfa

AF:

0.0162

Hom.:

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

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.38

CADD

Benign

7.2

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

MutationTaster

Benign

1.0

P;P;P;P;P

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over