dbSNP rs11900747: INHBB:p.Ser47Pro (chr2-120346327-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002193.4(INHBB):c.139T>C(p.Ser47Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000081 in 1,234,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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: not found (cov: 32)

Exomes 𝑓: 8.1e-7 ( 0 hom. )

Consequence

INHBB
NM_002193.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0820

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1724981).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002193.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INHBB	NM_002193.4	MANE Select	c.139T>C	p.Ser47Pro	missense	Exon 1 of 2	NP_002184.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INHBB	ENST00000295228.4	TSL:1 MANE Select	c.139T>C	p.Ser47Pro	missense	Exon 1 of 2	ENSP00000295228.3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.10e-7

AC:

AN:

1234964

Hom.:

Cov.:

AF XY:

0.00000167

AC XY:

AN XY:

600096

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

23988

American (AMR)

AF:

0.00

AC:

AN:

13378

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17842

East Asian (EAS)

AF:

0.00

AC:

AN:

27456

South Asian (SAS)

AF:

0.00

AC:

AN:

55838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33690

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3510

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1008604

Other (OTH)

AF:

0.0000197

AC:

AN:

50658

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.31

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.19

M_CAP

Pathogenic

0.90

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.0

PhyloP100

-0.082

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.82

REVEL

Benign

0.24

Sift

Benign

0.046

Sift4G

Benign

0.20

Polyphen

0.0040

Vest4

0.069

MutPred

0.20

Loss of phosphorylation at S47 (P = 0.0054)

MVP

0.45

MPC

2.0

ClinPred

0.10

GERP RS

2.5

PromoterAI

-0.088

Neutral

(source)

Varity_R

0.20

gMVP

0.14

Mutation Taster

=84/16

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over