dbSNP rs11893842: INHA:n.286-2443A>G (chr2-219572251-A-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PP3_ModerateBA1

The ENST00000489456.1(INHA):n.286-2443A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 1,396,758 control chromosomes in the GnomAD database, including 139,940 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 0.45 ( 15184 hom., cov: 32)

Exomes 𝑓: 0.44 ( 124756 hom. )

Consequence

INHA
ENST00000489456.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.415

Publications

17 publications found

Variant links:

Genes affected

INHA (HGNC:6065): (inhibin subunit alpha) This gene encodes a member of the TGF-beta (transforming growth factor-beta) superfamily of proteins. The encoded preproprotein is proteolytically processed to generate multiple peptide products, including the alpha subunit of the inhibin A and B protein complexes. These complexes negatively regulate follicle stimulating hormone secretion from the pituitary gland. Inhibins have also been implicated in regulating numerous cellular processes including cell proliferation, apoptosis, immune response and hormone secretion. Mutations in this gene may be associated with male infertility and premature ovarian failure in female human patients. [provided by RefSeq, Aug 2016]

INHA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INHA	NM_002191.4 link	c.-124A>G		upstream_gene_variant		ENST00000243786.3	NP_002182.1	P05111

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INHA	ENST00000489456.1 link	n.286-2443A>G		intron_variant	Intron 1 of 1	2
INHA	ENST00000243786.3 link	c.-124A>G		upstream_gene_variant		1	NM_002191.4	ENSP00000243786.2		P05111

Frequencies

GnomAD3 genomes

AF:

0.450

AC:

67785

AN:

150570

Hom.:

15177

Cov.:

show subpopulations

Gnomad AFR

AF:

0.441

Gnomad AMI

AF:

0.298

Gnomad AMR

AF:

0.470

Gnomad ASJ

AF:

0.489

Gnomad EAS

AF:

0.422

Gnomad SAS

AF:

0.416

Gnomad FIN

AF:

0.451

Gnomad MID

AF:

0.458

Gnomad NFE

AF:

0.455

Gnomad OTH

AF:

0.477

GnomAD4 exome

AF:

0.445

AC:

554180

AN:

1246058

Hom.:

124756

Cov.:

AF XY:

0.443

AC XY:

278191

AN XY:

628430

show subpopulations

African (AFR)

AF:

0.444

AC:

13098

AN:

29532

American (AMR)

AF:

0.469

AC:

20526

AN:

43774

Ashkenazi Jewish (ASJ)

AF:

0.476

AC:

11684

AN:

24562

East Asian (EAS)

AF:

0.383

AC:

14719

AN:

38478

South Asian (SAS)

AF:

0.392

AC:

31744

AN:

81062

European-Finnish (FIN)

AF:

0.437

AC:

22754

AN:

52018

Middle Eastern (MID)

AF:

0.457

AC:

1742

AN:

3810

European-Non Finnish (NFE)

AF:

0.450

AC:

414217

AN:

919792

Other (OTH)

AF:

0.447

AC:

23696

AN:

53030

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

14975

29949

44924

59898

74873

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11568

23136

34704

46272

57840

<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:

0.450

AC:

67830

AN:

150700

Hom.:

15184

Cov.:

AF XY:

0.449

AC XY:

33053

AN XY:

73626

show subpopulations

African (AFR)

AF:

0.441

AC:

18167

AN:

41184

American (AMR)

AF:

0.469

AC:

7145

AN:

15222

Ashkenazi Jewish (ASJ)

AF:

0.489

AC:

1691

AN:

3456

East Asian (EAS)

AF:

0.421

AC:

2086

AN:

4956

South Asian (SAS)

AF:

0.416

AC:

1926

AN:

4634

European-Finnish (FIN)

AF:

0.451

AC:

4654

AN:

10330

Middle Eastern (MID)

AF:

0.459

AC:

133

AN:

290

European-Non Finnish (NFE)

AF:

0.455

AC:

30769

AN:

67626

Other (OTH)

AF:

0.471

AC:

990

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1964

3928

5893

7857

9821

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

626

1252

1878

2504

3130

<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:

0.432

Hom.:

2014

Bravo

AF:

0.453

Asia WGS

AF:

0.366

AC:

1273

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

8.2

(source)

DANN

Benign

0.84

PhyloP100

0.41

PromoterAI

0.0064

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.89

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.89

Position offset: -1

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