Variant chr7-41689979-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_002192.4(INHBA):c.952G>A(p.Val318Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.000011 ( 0 hom. )

Consequence

INHBA
NM_002192.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.56

Variant links:

Genes affected

INHBA (HGNC:6066): (inhibin subunit beta A) 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. The encoded protein also plays a role in eye, tooth and testis development. Elevated expression of this gene may be associated with cancer cachexia in human patients. [provided by RefSeq, Aug 2016]

INHBA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.19091982).

BS2

High AC in GnomAdExome4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
INHBA	NM_002192.4 linkuse as main transcript	c.952G>A	p.Val318Ile	missense_variant	3/3	ENST00000242208.5	NP_002183.1
INHBA	XM_017012174.2 linkuse as main transcript	c.952G>A	p.Val318Ile	missense_variant	3/3		XP_016867663.2
INHBA	XM_047420335.1 linkuse as main transcript	c.952G>A	p.Val318Ile	missense_variant	4/4		XP_047276291.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INHBA	ENST00000242208.5 linkuse as main transcript	c.952G>A	p.Val318Ile	missense_variant	3/3	1	NM_002192.4	ENSP00000242208	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251190

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135774

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461744

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

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 07, 2022

The c.952G>A (p.V318I) alteration is located in exon 3 (coding exon 2) of the INHBA gene. This alteration results from a G to A substitution at nucleotide position 952, causing the valine (V) at amino acid position 318 to be replaced by an isoleucine (I). 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

0.097

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.43

T;T;T

Eigen

Benign

0.046

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.87

.;.;D

M_CAP

Benign

0.024

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.4

L;L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.44

N;N;.

REVEL

Benign

0.12

Sift

Benign

0.22

T;T;.

Sift4G

Benign

0.32

T;T;.

Polyphen

0.042

B;B;B

Vest4

0.13

MutPred

0.34

Loss of methylation at K317 (P = 0.1046);Loss of methylation at K317 (P = 0.1046);Loss of methylation at K317 (P = 0.1046);

MVP

0.35

MPC

0.63

ClinPred

0.17

GERP RS

6.0

Varity_R

0.21

gMVP

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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