rs7588807

Positions:

• chr2-219574380-G-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
INHA	NM_002191.4	c.269-314G>T		intron_variant		ENST00000243786.3	NP_002182.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INHA	ENST00000243786.3	c.269-314G>T		intron_variant		1	NM_002191.4	ENSP00000243786	P1
INHA	ENST00000489456.1	n.286-314G>T		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.423

Gnomad4 AMR AF: 0.445

Gnomad4 ASJ AF: 0.461

Gnomad4 EAS AF: 0.579

Gnomad4 SAS AF: 0.458

Gnomad4 FIN AF: 0.564

Gnomad4 NFE AF: 0.501

Gnomad4 OTH AF: 0.467

Alfa AF: 0.495 Hom.: 38534

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs7588807; hg19: chr2-220439102;