dbSNP rs12720063: INHA:p.Ala177Ala (chr2-219574956-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_002191.4(INHA):c.531C>T(p.Ala177Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 1,613,948 control chromosomes in the GnomAD database, including 32,126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.18 ( 2568 hom., cov: 33)

Exomes 𝑓: 0.20 ( 29558 hom. )

Consequence

INHA
NM_002191.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -8.89

Publications

11 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: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 2-219574956-C-T is Benign according to our data. Variant chr2-219574956-C-T is described in ClinVar as Benign. ClinVar VariationId is 3055288.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-8.89 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002191.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INHA	NM_002191.4	MANE Select	c.531C>T	p.Ala177Ala	synonymous	Exon 2 of 2	NP_002182.1	P05111

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INHA	ENST00000243786.3	TSL:1 MANE Select	c.531C>T	p.Ala177Ala	synonymous	Exon 2 of 2	ENSP00000243786.2	P05111
	INHA	ENST00000489456.1	TSL:2	n.548C>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.176

AC:

26829

AN:

152146

Hom.:

2569

Cov.:

show subpopulations

Gnomad AFR

AF:

0.113

Gnomad AMI

AF:

0.197

Gnomad AMR

AF:

0.235

Gnomad ASJ

AF:

0.189

Gnomad EAS

AF:

0.194

Gnomad SAS

AF:

0.0921

Gnomad FIN

AF:

0.196

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.203

Gnomad OTH

AF:

0.179

GnomAD2 exomes

AF:

0.188

AC:

47088

AN:

250986

AF XY:

0.183

show subpopulations

Gnomad AFR exome

AF:

0.109

Gnomad AMR exome

AF:

0.254

Gnomad ASJ exome

AF:

0.176

Gnomad EAS exome

AF:

0.197

Gnomad FIN exome

AF:

0.198

Gnomad NFE exome

AF:

0.202

Gnomad OTH exome

AF:

0.193

GnomAD4 exome

AF:

0.198

AC:

289084

AN:

1461682

Hom.:

29558

Cov.:

AF XY:

0.194

AC XY:

141126

AN XY:

727158

show subpopulations

African (AFR)

AF:

0.108

AC:

3613

AN:

33480

American (AMR)

AF:

0.249

AC:

11152

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.175

AC:

4575

AN:

26132

East Asian (EAS)

AF:

0.169

AC:

6709

AN:

39700

South Asian (SAS)

AF:

0.0943

AC:

8131

AN:

86258

European-Finnish (FIN)

AF:

0.197

AC:

10476

AN:

53240

Middle Eastern (MID)

AF:

0.163

AC:

938

AN:

5768

European-Non Finnish (NFE)

AF:

0.209

AC:

232126

AN:

1111986

Other (OTH)

AF:

0.188

AC:

11364

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

16448

32896

49343

65791

82239

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8090

16180

24270

32360

40450

<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:

0.176

AC:

26840

AN:

152266

Hom.:

2568

Cov.:

AF XY:

0.176

AC XY:

13077

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.113

AC:

4689

AN:

41570

American (AMR)

AF:

0.235

AC:

3589

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.189

AC:

656

AN:

3468

East Asian (EAS)

AF:

0.194

AC:

1003

AN:

5178

South Asian (SAS)

AF:

0.0934

AC:

451

AN:

4830

European-Finnish (FIN)

AF:

0.196

AC:

2077

AN:

10600

Middle Eastern (MID)

AF:

0.156

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.203

AC:

13775

AN:

68006

Other (OTH)

AF:

0.177

AC:

375

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1197

2393

3590

4786

5983

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

292

584

876

1168

1460

<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:

0.168

Hom.:

1177

Bravo

AF:

0.180

Asia WGS

AF:

0.122

AC:

425

AN:

3478

EpiCase

AF:

0.203

EpiControl

AF:

0.200

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

INHA-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.58

(source)

DANN

Benign

0.71

PhyloP100

-8.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over