Variant chr12-51951807-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_004302.5(ACVR1B):c.64G>A(p.Gly22Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ACVR1B
NM_004302.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.271

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant where missense usually causes diseases, ACVR1B

BP4

Computational evidence support a benign effect (MetaRNN=0.22228605).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACVR1B	NM_004302.5 linkuse as main transcript	c.64G>A	p.Gly22Ser	missense_variant	1/9	ENST00000257963.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACVR1B	ENST00000257963.9 linkuse as main transcript	c.64G>A	p.Gly22Ser	missense_variant	1/9	1	NM_004302.5	P1	P36896-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1133118

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

540142

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 11, 2024

The c.64G>A (p.G22S) alteration is located in exon 1 (coding exon 1) of the ACVR1B gene. This alteration results from a G to A substitution at nucleotide position 64, causing the glycine (G) at amino acid position 22 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.033

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.21

T;.;.;.

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.51

T;T;T;T

M_CAP

Pathogenic

0.97

MetaRNN

Benign

0.22

T;T;T;T

MetaSVM

Uncertain

-0.17

MutationAssessor

Benign

0.0

N;N;N;N

MutationTaster

Benign

0.73

N;N;N;N

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

0.55

N;N;N;N

REVEL

Benign

0.24

Sift

Benign

0.82

T;T;T;T

Sift4G

Benign

0.47

T;T;T;T

Polyphen

1.0

D;B;D;B

Vest4

0.19

MutPred

0.36

Gain of catalytic residue at S21 (P = 2e-04);Gain of catalytic residue at S21 (P = 2e-04);Gain of catalytic residue at S21 (P = 2e-04);Gain of catalytic residue at S21 (P = 2e-04);

MVP

0.89

MPC

0.99

ClinPred

0.30

GERP RS

2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.047

gMVP

0.59

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over