Variant 12-57456130-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031479.5(INHBE):c.335A>G(p.His112Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,354 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

INHBE
NM_031479.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.850

Variant links:

Genes affected

INHBE (HGNC:24029): (inhibin subunit beta E) This gene encodes a member of the TGF-beta (transforming growth factor-beta) superfamily of proteins. The encoded preproprotein is proteolytically processed to generate an inhibin beta subunit. Inhibins have been implicated in regulating numerous cellular processes including cell proliferation, apoptosis, immune response and hormone secretion. This gene may be upregulated under conditions of endoplasmic reticulum stress, and this protein may inhibit cellular proliferation and growth in pancreas and liver. [provided by RefSeq, Sep 2016]

INHBE links:

INHBE (HGNC:):

INHBE links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15715173).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INHBE	NM_031479.5 linkuse as main transcript	c.335A>G	p.His112Arg	missense_variant	2/2	ENST00000266646.3	NP_113667.1	P58166

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
INHBE	ENST00000266646.3 linkuse as main transcript	c.335A>G	p.His112Arg	missense_variant	2/2	1	NM_031479.5	ENSP00000266646.2	P58166
INHBE	ENST00000551553.1 linkuse as main transcript	n.254A>G		non_coding_transcript_exon_variant	2/3	1
INHBE	ENST00000547970.1 linkuse as main transcript	n.404A>G		non_coding_transcript_exon_variant	3/3	3
INHBE	ENST00000553033.1 linkuse as main transcript	n.61A>G		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000280

AC:

AN:

250368

Hom.:

AF XY:

0.0000370

AC XY:

AN XY:

135288

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461354

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

726962

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000330

AC:

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

Jun 26, 2023

The c.335A>G (p.H112R) alteration is located in exon 2 (coding exon 2) of the INHBE gene. This alteration results from a A to G substitution at nucleotide position 335, causing the histidine (H) at amino acid position 112 to be replaced by an arginine (R). 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

0.066

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.81

DEOGEN2

Benign

0.40

.;T

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.39

T;T

M_CAP

Benign

0.057

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-0.75

MutationAssessor

Benign

1.7

.;L

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.86

N;N

REVEL

Benign

0.095

Sift

Uncertain

0.017

D;D

Sift4G

Benign

0.34

T;T

Polyphen

0.058

.;B

Vest4

0.039

MutPred

0.49

.;Gain of catalytic residue at R117 (P = 6e-04);

MVP

0.82

MPC

0.30

ClinPred

0.046

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.17

gMVP

0.24

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over