Genetic Variant INHBB:p.Ser47Ala (chr2-120346327-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002193.4(INHBB):c.139T>G(p.Ser47Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,385,044 control chromosomes in the GnomAD database, including 13,016 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.18 ( 4335 hom., cov: 32)

Exomes 𝑓: 0.091 ( 8681 hom. )

Consequence

INHBB
NM_002193.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0820

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:

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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=9.382069E-4).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INHBB	NM_002193.4 link	c.139T>G	p.Ser47Ala	missense_variant	Exon 1 of 2	ENST00000295228.4	NP_002184.2	P09529

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INHBB	ENST00000295228.4 link	c.139T>G	p.Ser47Ala	missense_variant	Exon 1 of 2	1	NM_002193.4	ENSP00000295228.3		P09529

Frequencies

GnomAD3 genomes

AF:

0.183

AC:

27518

AN:

150426

Hom.:

4322

Cov.:

show subpopulations

Gnomad AFR

AF:

0.419

Gnomad AMI

AF:

0.0330

Gnomad AMR

AF:

0.105

Gnomad ASJ

AF:

0.162

Gnomad EAS

AF:

0.163

Gnomad SAS

AF:

0.300

Gnomad FIN

AF:

0.0541

Gnomad MID

AF:

0.163

Gnomad NFE

AF:

0.0727

Gnomad OTH

AF:

0.157

GnomAD3 exomes

AF:

0.0736

AC:

1265

AN:

17196

Hom.:

AF XY:

0.0814

AC XY:

781

AN XY:

9594

show subpopulations

Gnomad AFR exome

AF:

0.338

Gnomad AMR exome

AF:

0.0361

Gnomad ASJ exome

AF:

0.104

Gnomad EAS exome

AF:

0.119

Gnomad SAS exome

AF:

0.188

Gnomad FIN exome

AF:

0.0356

Gnomad NFE exome

AF:

0.0503

Gnomad OTH exome

AF:

0.0959

GnomAD4 exome

AF:

0.0905

AC:

111742

AN:

1234524

Hom.:

8681

Cov.:

AF XY:

0.0944

AC XY:

56597

AN XY:

599822

show subpopulations

Gnomad4 AFR exome

AF:

0.441

Gnomad4 AMR exome

AF:

0.0655

Gnomad4 ASJ exome

AF:

0.155

Gnomad4 EAS exome

AF:

0.218

Gnomad4 SAS exome

AF:

0.281

Gnomad4 FIN exome

AF:

0.0494

Gnomad4 NFE exome

AF:

0.0670

Gnomad4 OTH exome

AF:

0.120

GnomAD4 genome

AF:

0.183

AC:

27562

AN:

150520

Hom.:

4335

Cov.:

AF XY:

0.184

AC XY:

13510

AN XY:

73452

show subpopulations

Gnomad4 AFR

AF:

0.420

Gnomad4 AMR

AF:

0.104

Gnomad4 ASJ

AF:

0.162

Gnomad4 EAS

AF:

0.162

Gnomad4 SAS

AF:

0.299

Gnomad4 FIN

AF:

0.0541

Gnomad4 NFE

AF:

0.0727

Gnomad4 OTH

AF:

0.160

Alfa

AF:

0.125

Hom.:

287

Bravo

AF:

0.190

ExAC

AF:

0.0464

AC:

2674

Asia WGS

AF:

0.275

AC:

940

AN:

3428

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.38

DEOGEN2

Benign

0.26

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.067

LIST_S2

Benign

0.091

MetaRNN

Benign

0.00094

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

0.24

REVEL

Benign

0.22

Sift

Benign

0.64

Sift4G

Benign

0.96

Polyphen

0.0

Vest4

0.016

MPC

1.4

ClinPred

0.00018

GERP RS

2.5

Varity_R

0.071

gMVP

0.079

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