2-219574956-C-T

Variant names:

• chr2-219574956-C-T
• rs12720063
• NM_002191.4:c.531C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

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
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -8.89
• Publications: 11 publications found

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]

ACMG classification

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

Selected	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

Ensembl Transcripts

Selected	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
	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.: 33

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

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.: 34 AF XY: 0.194 AC XY: 141126 AN XY: 727158

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

GnomAD4 genome AF: 0.176 AC: 26840 AN: 152266 Hom.: 2568 Cov.: 33 AF XY: 0.176 AC XY: 13077 AN XY: 74444

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: 46 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13775 AN: 68006

Other (OTH) AF: 0.177 AC: 375 AN: 2114

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 as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	INHA-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.58
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)

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

Other links and lift over

dbSNP: rs12720063; hg19: chr2-220439678; COSMIC: COSV54715323; COSMIC: COSV54715323;