rs507562

Variant names:

• chr12-57455985-C-G
• rs507562
• NM_031479.5:c.299-109C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-57455985-C-G
• chr12-57455985-C-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031479.5. 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
	INHBE	NM_031479.5	MANE Select	c.299-109C>G		intron	N/A	NP_113667.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INHBE	ENST00000266646.3	TSL:1 MANE Select	c.299-109C>G		intron	N/A	ENSP00000266646.2
	INHBE	ENST00000551553.1	TSL:1	n.218-109C>G		intron	N/A
	INHBE	ENST00000553033.1	TSL:4	n.14C>G		non_coding_transcript_exon	Exon 1 of 2

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

African (AFR) AF: 0.508 AC: 14823 AN: 29174

American (AMR) AF: 0.226 AC: 8017 AN: 35442

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 4525 AN: 20442

East Asian (EAS) AF: 0.316 AC: 12180 AN: 38592

South Asian (SAS) AF: 0.428 AC: 30544 AN: 71384

European-Finnish (FIN) AF: 0.346 AC: 14312 AN: 41404

Middle Eastern (MID) AF: 0.190 AC: 947 AN: 4992

European-Non Finnish (NFE) AF: 0.249 AC: 245142 AN: 986094

Other (OTH) AF: 0.293 AC: 15713 AN: 53712

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

African (AFR) AF: 0.497 AC: 20560 AN: 41358

American (AMR) AF: 0.273 AC: 4165 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 750 AN: 3468

East Asian (EAS) AF: 0.328 AC: 1691 AN: 5154

South Asian (SAS) AF: 0.432 AC: 2082 AN: 4814

European-Finnish (FIN) AF: 0.372 AC: 3925 AN: 10552

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.246 AC: 16699 AN: 67928

Other (OTH) AF: 0.297 AC: 624 AN: 2104

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.28
DANN	Benign	0.46
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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