dbSNP rs45624437: INHBB:c.*732T>C (chr2-120350606-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_002193.4(INHBB):c.*732T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 148,940 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.011 ( 20 hom., cov: 33)

Exomes 𝑓: 0.0094 ( 0 hom. )

Consequence

INHBB
NM_002193.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.812

Publications

4 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0107 (1590/148834) while in subpopulation AMR AF = 0.0244 (365/14952). AF 95% confidence interval is 0.0223. There are 20 homozygotes in GnomAd4. There are 837 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 1590 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INHBB	NM_002193.4 link	c.*732T>C		3_prime_UTR_variant	Exon 2 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.*732T>C		3_prime_UTR_variant	Exon 2 of 2	1	NM_002193.4	ENSP00000295228.3		P09529

Frequencies

GnomAD3 genomes

AF:

0.0107

AC:

1590

AN:

148722

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00227

Gnomad AMI

AF:

0.0210

Gnomad AMR

AF:

0.0244

Gnomad ASJ

AF:

0.000580

Gnomad EAS

AF:

0.000395

Gnomad SAS

AF:

0.00234

Gnomad FIN

AF:

0.0391

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0103

Gnomad OTH

AF:

0.00740

GnomAD4 exome

AF:

0.00943

AC:

AN:

106

Hom.:

Cov.:

AF XY:

0.0200

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.0217

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

AF:

0.0107

AC:

1590

AN:

148834

Hom.:

Cov.:

AF XY:

0.0115

AC XY:

837

AN XY:

72484

show subpopulations

African (AFR)

AF:

0.00226

AC:

AN:

40188

American (AMR)

AF:

0.0244

AC:

365

AN:

14952

Ashkenazi Jewish (ASJ)

AF:

0.000580

AC:

AN:

3448

East Asian (EAS)

AF:

0.000396

AC:

AN:

5048

South Asian (SAS)

AF:

0.00235

AC:

AN:

4690

European-Finnish (FIN)

AF:

0.0391

AC:

390

AN:

9976

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0103

AC:

695

AN:

67288

Other (OTH)

AF:

0.00732

AC:

AN:

2050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

156

235

313

391

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0117

Hom.:

Bravo

AF:

0.0105

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

(source)

DANN

Benign

0.79

PhyloP100

0.81

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over