rs507562

chr12-57455985-C-Gchr12-57455985-C-T

Variant summary

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

The NM_031479.5(INHBE):c.299-109C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 1,433,078 control chromosomes in the GnomAD database, including 59,385 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 0.33 (9446 hom., cov: 31)
  • Exomes 𝑓: 0.27 (49939 hom.)
• Consequence: INHBE NM_031479.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22

Genes affected

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INHBE	NM_031479.5	c.299-109C>G		intron_variant		ENST00000266646.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INHBE	ENST00000266646.3	c.299-109C>G		intron_variant		1	NM_031479.5	P1
INHBE	ENST00000551553.1	n.218-109C>G		intron_variant, non_coding_transcript_variant		1
INHBE	ENST00000553033.1	n.14C>G		non_coding_transcript_exon_variant	1/2	4
INHBE	ENST00000547970.1	n.368-109C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50647 AN: 151724 Hom.: 9427 Cov.: 31

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.292

GnomAD4 exome AF: 0.270 AC: 346203 AN: 1281236 Hom.: 49939 Cov.: 20 AF XY: 0.274 AC XY: 173690 AN XY: 634830

Gnomad4 AFR exome AF: 0.508

Gnomad4 AMR exome AF: 0.226

Gnomad4 ASJ exome AF: 0.221

Gnomad4 EAS exome AF: 0.316

Gnomad4 SAS exome AF: 0.428

Gnomad4 FIN exome AF: 0.346

Gnomad4 NFE exome AF: 0.249

Gnomad4 OTH exome AF: 0.293

GnomAD4 genome AF: 0.334 AC: 50709 AN: 151842 Hom.: 9446 Cov.: 31 AF XY: 0.341 AC XY: 25301 AN XY: 74198

Gnomad4 AFR AF: 0.497

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.216

Gnomad4 EAS AF: 0.328

Gnomad4 SAS AF: 0.432

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.246

Gnomad4 OTH AF: 0.297

Alfa AF: 0.168 Hom.: 352

Bravo AF: 0.326

Asia WGS AF: 0.367 AC: 1274 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.28
Dann	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs507562; hg19: chr12-57849768; COSMIC: COSV56988578; COSMIC: COSV56988578;