12-57454856-G-A

Variant names:

• chr12-57454856-G-A
• rs3809114
• ENST00000551553.1:n.218-1238G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000551553.1(INHBE):​n.218-1238G>A variant causes a intron 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.18
• Publications: 28 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000551553.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INHBE	ENST00000551553.1	TSL:1	n.218-1238G>A		intron	N/A
	INHBE	ENST00000547970.1	TSL:3	n.154G>A		non_coding_transcript_exon	Exon 1 of 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

African (AFR) AF: 0.235 AC: 2004 AN: 8532

American (AMR) AF: 0.463 AC: 12563 AN: 27118

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 6138 AN: 10664

East Asian (EAS) AF: 0.320 AC: 2937 AN: 9168

South Asian (SAS) AF: 0.442 AC: 26376 AN: 59650

European-Finnish (FIN) AF: 0.461 AC: 5683 AN: 12334

Middle Eastern (MID) AF: 0.570 AC: 1507 AN: 2644

European-Non Finnish (NFE) AF: 0.558 AC: 88051 AN: 157752

Other (OTH) AF: 0.503 AC: 7090 AN: 14088

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

African (AFR) AF: 0.241 AC: 10002 AN: 41518

American (AMR) AF: 0.470 AC: 7190 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 1981 AN: 3470

East Asian (EAS) AF: 0.329 AC: 1701 AN: 5170

South Asian (SAS) AF: 0.423 AC: 2041 AN: 4830

European-Finnish (FIN) AF: 0.434 AC: 4593 AN: 10594

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.557 AC: 37873 AN: 67982

Other (OTH) AF: 0.474 AC: 1000 AN: 2110

Alfa AF: 0.515 Hom.: 50862

Bravo AF: 0.439

Asia WGS AF: 0.338 AC: 1180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.031
DANN	Benign	0.49
PhyloP100		-2.2
PromoterAI		-0.0052	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3809114; hg19: chr12-57848639;