rs7588807

Variant names:

• chr2-219574380-G-T
• rs7588807
• NM_002191.4:c.269-314G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002191.4(INHA):​c.269-314G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 151,920 control chromosomes in the GnomAD database, including 17,528 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 0.48 (17528 hom., cov: 32)
• Consequence: INHA NM_002191.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.789
• Publications: 19 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INHA	NM_002191.4	c.269-314G>T		intron_variant	Intron 1 of 1	ENST00000243786.3	NP_002182.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INHA	ENST00000243786.3	c.269-314G>T		intron_variant	Intron 1 of 1	1	NM_002191.4	ENSP00000243786.2
INHA	ENST00000489456.1	n.286-314G>T		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72741 AN: 151804 Hom.: 17506 Cov.: 32

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.578

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.462

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.479 AC: 72815 AN: 151920 Hom.: 17528 Cov.: 32 AF XY: 0.482 AC XY: 35784 AN XY: 74256

African (AFR) AF: 0.423 AC: 17504 AN: 41406

American (AMR) AF: 0.445 AC: 6800 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.461 AC: 1599 AN: 3466

East Asian (EAS) AF: 0.579 AC: 2997 AN: 5174

South Asian (SAS) AF: 0.458 AC: 2204 AN: 4812

European-Finnish (FIN) AF: 0.564 AC: 5923 AN: 10510

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.501 AC: 34069 AN: 67958

Other (OTH) AF: 0.467 AC: 987 AN: 2114

Alfa AF: 0.489 Hom.: 57762

Bravo AF: 0.467

Asia WGS AF: 0.556 AC: 1937 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.37
DANN	Benign	0.33
PhyloP100		-0.79
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7588807; hg19: chr2-220439102;