Genetic Variant INHA:c.-16C>T (chr2-219572359-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002191.4(INHA):c.-16C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 1,613,276 control chromosomes in the GnomAD database, including 32,804 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.18 ( 2677 hom., cov: 33)

Exomes 𝑓: 0.20 ( 30127 hom. )

Consequence

INHA
NM_002191.4 5_prime_UTR

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.694

Publications

32 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:

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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=-0.72).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INHA	NM_002191.4 link	c.-16C>T		5_prime_UTR_variant	Exon 1 of 2	ENST00000243786.3	NP_002182.1	P05111

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INHA	ENST00000243786.3 link	c.-16C>T		5_prime_UTR_variant	Exon 1 of 2	1	NM_002191.4	ENSP00000243786.2		P05111
INHA	ENST00000489456.1 link	n.286-2335C>T		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes

AF:

0.183

AC:

27837

AN:

152050

Hom.:

2680

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.199

Gnomad AMR

AF:

0.240

Gnomad ASJ

AF:

0.186

Gnomad EAS

AF:

0.194

Gnomad SAS

AF:

0.0911

Gnomad FIN

AF:

0.196

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.204

Gnomad OTH

AF:

0.183

GnomAD2 exomes

AF:

0.190

AC:

47742

AN:

251360

AF XY:

0.185

show subpopulations

Gnomad AFR exome

AF:

0.134

Gnomad AMR exome

AF:

0.257

Gnomad ASJ exome

AF:

0.171

Gnomad EAS exome

AF:

0.197

Gnomad FIN exome

AF:

0.198

Gnomad NFE exome

AF:

0.203

Gnomad OTH exome

AF:

0.193

GnomAD4 exome

AF:

0.200

AC:

291695

AN:

1461108

Hom.:

30127

Cov.:

AF XY:

0.196

AC XY:

142304

AN XY:

726856

show subpopulations

African (AFR)

AF:

0.134

AC:

4482

AN:

33458

American (AMR)

AF:

0.253

AC:

11337

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.170

AC:

4453

AN:

26136

East Asian (EAS)

AF:

0.169

AC:

6713

AN:

39700

South Asian (SAS)

AF:

0.0943

AC:

8127

AN:

86198

European-Finnish (FIN)

AF:

0.197

AC:

10507

AN:

53412

Middle Eastern (MID)

AF:

0.163

AC:

856

AN:

5262

European-Non Finnish (NFE)

AF:

0.210

AC:

233714

AN:

1111888

Other (OTH)

AF:

0.191

AC:

11506

AN:

60330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

13170

26340

39510

52680

65850

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8144

16288

24432

32576

40720

<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:

0.183

AC:

27842

AN:

152168

Hom.:

2677

Cov.:

AF XY:

0.182

AC XY:

13553

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.134

AC:

5560

AN:

41526

American (AMR)

AF:

0.240

AC:

3666

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.186

AC:

646

AN:

3472

East Asian (EAS)

AF:

0.194

AC:

1000

AN:

5166

South Asian (SAS)

AF:

0.0924

AC:

446

AN:

4828

European-Finnish (FIN)

AF:

0.196

AC:

2079

AN:

10596

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.204

AC:

13834

AN:

67968

Other (OTH)

AF:

0.182

AC:

383

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1166

2332

3499

4665

5831

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

296

592

888

1184

1480

<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:

0.191

Hom.:

762

Bravo

AF:

0.187

Asia WGS

AF:

0.127

AC:

441

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Jun 06, 2018

OMIM

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

DANN

Benign

0.88

PhyloP100

0.69

PromoterAI

-0.017

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=300/0

polymorphism (auto)

(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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over