Variant 2-120346571-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_002193.4(INHBB):c.383G>C(p.Gly128Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000199 in 1,479,320 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

INHBB
NM_002193.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.01

Variant links:

Genes affected

INHBB (HGNC:6067): (inhibin subunit beta B) This gene encodes a member of the TGF-beta (transforming growth factor-beta) superfamily of proteins. The encoded preproprotein is proteolytically processed to generate a subunit of the dimeric activin and inhibin protein complexes. These complexes activate and inhibit, respectively, follicle stimulating hormone secretion from the pituitary gland. Polymorphisms near this gene are associated with pre-eclampsia in female human patients. [provided by RefSeq, Aug 2016]

INHBB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.30356514).

BS2

High AC in GnomAd4 at 19 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INHBB	NM_002193.4 linkuse as main transcript	c.383G>C	p.Gly128Ala	missense_variant	1/2	ENST00000295228.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INHBB	ENST00000295228.4 linkuse as main transcript	c.383G>C	p.Gly128Ala	missense_variant	1/2	1	NM_002193.4	P1

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000644

AC:

AN:

124264

Hom.:

AF XY:

0.0000561

AC XY:

AN XY:

71324

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000601

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000111

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000208

AC:

276

AN:

1327124

Hom.:

Cov.:

AF XY:

0.000218

AC XY:

142

AN XY:

652542

show subpopulations

Gnomad4 AFR exome

AF:

0.0000739

Gnomad4 AMR exome

AF:

0.0000378

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:

0.000237

Gnomad4 OTH exome

AF:

0.000421

GnomAD4 genome

AF:

0.000125

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000136

ExAC

AF:

0.0000517

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

Jan 26, 2023

The c.383G>C (p.G128A) alteration is located in exon 1 (coding exon 1) of the INHBB gene. This alteration results from a G to C substitution at nucleotide position 383, causing the glycine (G) at amino acid position 128 to be replaced by an alanine (A). 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

0.19

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.30

Eigen

Benign

-0.067

Eigen_PC

Benign

-0.046

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.86

M_CAP

Pathogenic

0.63

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-1.4

REVEL

Benign

0.19

Sift

Benign

0.076

Sift4G

Benign

0.17

Polyphen

0.63

Vest4

0.29

MVP

0.68

MPC

1.4

ClinPred

0.18

GERP RS

3.1

Varity_R

0.25

gMVP

0.54

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