rs3809114

chr12-57454856-G-Achr12-57454856-G-C

Variant summary

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

The ENST00000551553.1(INHBE):n.218-1238G>A 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 0.483 in 454,126 control chromosomes in the GnomAD database, including 55,972 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 0.44 (16324 hom., cov: 33)
  • Exomes 𝑓: 0.50 (39648 hom.)
• Consequence: INHBE ENST00000551553.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.18

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INHBE	ENST00000551553.1	n.218-1238G>A		intron_variant, non_coding_transcript_variant		1
INHBE	ENST00000547970.1	n.154G>A		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67208 AN: 152058 Hom.: 16321 Cov.: 33

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.479

GnomAD4 exome AF: 0.505 AC: 152349 AN: 301950 Hom.: 39648 Cov.: 0 AF XY: 0.502 AC XY: 86242 AN XY: 171956

Gnomad4 AFR exome AF: 0.235

Gnomad4 AMR exome AF: 0.463

Gnomad4 ASJ exome AF: 0.576

Gnomad4 EAS exome AF: 0.320

Gnomad4 SAS exome AF: 0.442

Gnomad4 FIN exome AF: 0.461

Gnomad4 NFE exome AF: 0.558

Gnomad4 OTH exome AF: 0.503

GnomAD4 genome AF: 0.442 AC: 67216 AN: 152176 Hom.: 16324 Cov.: 33 AF XY: 0.435 AC XY: 32385 AN XY: 74388

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.470

Gnomad4 ASJ AF: 0.571

Gnomad4 EAS AF: 0.329

Gnomad4 SAS AF: 0.423

Gnomad4 FIN AF: 0.434

Gnomad4 NFE AF: 0.557

Gnomad4 OTH AF: 0.474

Alfa AF: 0.542 Hom.: 32979

Bravo AF: 0.439

Asia WGS AF: 0.338 AC: 1180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.031
Dann	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3809114; hg19: chr12-57848639;