chr2-219572251-A-G

Position:

• chr2-219572251-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000489456.1(INHA):​n.286-2443A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 1,396,758 control chromosomes in the GnomAD database, including 139,940 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 0.45 (15184 hom., cov: 32)
  • Exomes 𝑓: 0.44 (124756 hom.)
• Consequence: INHA ENST00000489456.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.415

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INHA	ENST00000489456.1	n.286-2443A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.450 AC: 67785 AN: 150570 Hom.: 15177 Cov.: 32

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.458

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.477

GnomAD4 exome AF: 0.445 AC: 554180 AN: 1246058 Hom.: 124756 Cov.: 18 AF XY: 0.443 AC XY: 278191 AN XY: 628430

Gnomad4 AFR exome AF: 0.444

Gnomad4 AMR exome AF: 0.469

Gnomad4 ASJ exome AF: 0.476

Gnomad4 EAS exome AF: 0.383

Gnomad4 SAS exome AF: 0.392

Gnomad4 FIN exome AF: 0.437

Gnomad4 NFE exome AF: 0.450

Gnomad4 OTH exome AF: 0.447

GnomAD4 genome AF: 0.450 AC: 67830 AN: 150700 Hom.: 15184 Cov.: 32 AF XY: 0.449 AC XY: 33053 AN XY: 73626

Gnomad4 AFR AF: 0.441

Gnomad4 AMR AF: 0.469

Gnomad4 ASJ AF: 0.489

Gnomad4 EAS AF: 0.421

Gnomad4 SAS AF: 0.416

Gnomad4 FIN AF: 0.451

Gnomad4 NFE AF: 0.455

Gnomad4 OTH AF: 0.471

Alfa AF: 0.432 Hom.: 2014

Bravo AF: 0.453

Asia WGS AF: 0.366 AC: 1273 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	8.2
DANN	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.89		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.89		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11893842; hg19: chr2-220436973; COSMIC: COSV54721582; COSMIC: COSV54721582;