dbSNP rs3809114: INHBE:n.218-1238G>A (chr12-57454856-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000551553.1(INHBE):n.218-1238G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 454,126 control chromosomes in the GnomAD database, including 55,972 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 0.44 ( 16324 hom., cov: 33)

Exomes 𝑓: 0.50 ( 39648 hom. )

Consequence

INHBE
ENST00000551553.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.18

Publications

28 publications found

Variant links:

Genes affected

INHBE (HGNC:24029): (inhibin subunit beta E) This gene encodes a member of the TGF-beta (transforming growth factor-beta) superfamily of proteins. The encoded preproprotein is proteolytically processed to generate an inhibin beta subunit. Inhibins have been implicated in regulating numerous cellular processes including cell proliferation, apoptosis, immune response and hormone secretion. This gene may be upregulated under conditions of endoplasmic reticulum stress, and this protein may inhibit cellular proliferation and growth in pancreas and liver. [provided by RefSeq, Sep 2016]

INHBE links:

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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=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INHBE	ENST00000551553.1 link	n.218-1238G>A		intron_variant	Intron 1 of 2	1
INHBE	ENST00000547970.1 link	n.154G>A		non_coding_transcript_exon_variant	Exon 1 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.442

AC:

67208

AN:

152058

Hom.:

16321

Cov.:

show subpopulations

Gnomad AFR

AF:

0.241

Gnomad AMI

AF:

0.702

Gnomad AMR

AF:

0.470

Gnomad ASJ

AF:

0.571

Gnomad EAS

AF:

0.328

Gnomad SAS

AF:

0.423

Gnomad FIN

AF:

0.434

Gnomad MID

AF:

0.677

Gnomad NFE

AF:

0.557

Gnomad OTH

AF:

0.479

GnomAD4 exome

AF:

0.505

AC:

152349

AN:

301950

Hom.:

39648

Cov.:

AF XY:

0.502

AC XY:

86242

AN XY:

171956

show subpopulations

African (AFR)

AF:

0.235

AC:

2004

AN:

8532

American (AMR)

AF:

0.463

AC:

12563

AN:

27118

Ashkenazi Jewish (ASJ)

AF:

0.576

AC:

6138

AN:

10664

East Asian (EAS)

AF:

0.320

AC:

2937

AN:

9168

South Asian (SAS)

AF:

0.442

AC:

26376

AN:

59650

European-Finnish (FIN)

AF:

0.461

AC:

5683

AN:

12334

Middle Eastern (MID)

AF:

0.570

AC:

1507

AN:

2644

European-Non Finnish (NFE)

AF:

0.558

AC:

88051

AN:

157752

Other (OTH)

AF:

0.503

AC:

7090

AN:

14088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

4102

8204

12306

16408

20510

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

432

864

1296

1728

2160

<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:

0.442

AC:

67216

AN:

152176

Hom.:

16324

Cov.:

AF XY:

0.435

AC XY:

32385

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.241

AC:

10002

AN:

41518

American (AMR)

AF:

0.470

AC:

7190

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.571

AC:

1981

AN:

3470

East Asian (EAS)

AF:

0.329

AC:

1701

AN:

5170

South Asian (SAS)

AF:

0.423

AC:

2041

AN:

4830

European-Finnish (FIN)

AF:

0.434

AC:

4593

AN:

10594

Middle Eastern (MID)

AF:

0.673

AC:

198

AN:

294

European-Non Finnish (NFE)

AF:

0.557

AC:

37873

AN:

67982

Other (OTH)

AF:

0.474

AC:

1000

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1858

3716

5573

7431

9289

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

614

1228

1842

2456

3070

<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:

0.515

Hom.:

50862

Bravo

AF:

0.439

Asia WGS

AF:

0.338

AC:

1180

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.031

(source)

DANN

Benign

0.49

PhyloP100

-2.2

PromoterAI

-0.0052

Neutral

(source)

Splicing

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