12-57459370-G-C

Variant names:

• chr12-57459370-G-C
• rs2242578
• ENST00000656936.1:n.268C>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000656936.1(ENSG00000287200):​n.268C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 152,218 control chromosomes in the GnomAD database, including 27,031 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 0.59 (26960 hom., cov: 30)
  • Exomes 𝑓: 0.63 (71 hom.)
• Consequence: ENSG00000287200 ENST00000656936.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240

Genes affected

ENSG00000287200 (HGNC:):

INHBE (HGNC:24029): (inhibin subunit beta E) This gene encodes a member of the TGF-beta (transforming growth factor-beta) superfamily of proteins. The encoded preproprotein is proteolytically processed to generate an inhibin beta subunit. Inhibins have been implicated in regulating numerous cellular processes including cell proliferation, apoptosis, immune response and hormone secretion. This gene may be upregulated under conditions of endoplasmic reticulum stress, and this protein may inhibit cellular proliferation and growth in pancreas and liver. [provided by RefSeq, Sep 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124902947	XR_007063335.1	n.422C>G		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000287200	ENST00000656936.1	n.268C>G		non_coding_transcript_exon_variant	Exon 2 of 2
INHBE	ENST00000551553.1	n.*90G>C		downstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89740 AN: 151736 Hom.: 26951 Cov.: 30

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.631

GnomAD4 exome AF: 0.626 AC: 228 AN: 364 Hom.: 71 AF XY: 0.650 AC XY: 156 AN XY: 240

Gnomad4 AFR exome AF: 0.583

Gnomad4 AMR exome AF: 1.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.530

Gnomad4 NFE exome AF: 0.691

Gnomad4 OTH exome AF: 0.714

GnomAD4 genome AF: 0.591 AC: 89764 AN: 151854 Hom.: 26960 Cov.: 30 AF XY: 0.584 AC XY: 43301 AN XY: 74200

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.580

Gnomad4 ASJ AF: 0.669

Gnomad4 EAS AF: 0.524

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.525

Gnomad4 NFE AF: 0.659

Gnomad4 OTH AF: 0.625

Alfa AF: 0.474 Hom.: 1257

Bravo AF: 0.593

Asia WGS AF: 0.469 AC: 1634 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.9
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2242578; hg19: chr12-57853153;