rs12432593

Variant names:

• chr14-34262386-C-A
• rs12432593
• ENST00000551935.5:n.60-92740G>T

Your query was ambiguous. Multiple possible variants found:

• chr14-34262386-C-A
• chr14-34262386-C-G

Variant summary

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

The ENST00000551935.5(EGLN3):​n.60-92740G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 151,832 control chromosomes in the GnomAD database, including 18,954 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 0.50 (18954 hom., cov: 31)
• Consequence: EGLN3 ENST00000551935.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.555
• Publications: 1 publications found

Genes affected

EGLN3 (HGNC:14661): (egl-9 family hypoxia inducible factor 3) Enables peptidyl-proline 4-dioxygenase activity. Involved in several processes, including activation of cysteine-type endopeptidase activity involved in apoptotic process; peptidyl-proline hydroxylation to 4-hydroxy-L-proline; and response to hypoxia. Located in cytosol and nucleus. Implicated in renal cell carcinoma. Biomarker of clear cell renal cell carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGLN3	ENST00000551935.5	n.60-92740G>T		intron_variant	Intron 1 of 4	4

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75365 AN: 151714 Hom.: 18933 Cov.: 31

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.375

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.660

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.538

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.497 AC: 75441 AN: 151832 Hom.: 18954 Cov.: 31 AF XY: 0.500 AC XY: 37126 AN XY: 74194

African (AFR) AF: 0.450 AC: 18639 AN: 41404

American (AMR) AF: 0.581 AC: 8863 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 1721 AN: 3468

East Asian (EAS) AF: 0.659 AC: 3392 AN: 5146

South Asian (SAS) AF: 0.542 AC: 2599 AN: 4798

European-Finnish (FIN) AF: 0.521 AC: 5495 AN: 10538

Middle Eastern (MID) AF: 0.455 AC: 133 AN: 292

European-Non Finnish (NFE) AF: 0.488 AC: 33113 AN: 67924

Other (OTH) AF: 0.543 AC: 1144 AN: 2106

Alfa AF: 0.482 Hom.: 2939

Bravo AF: 0.497

Asia WGS AF: 0.626 AC: 2179 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.1
DANN	Benign	0.69
PhyloP100		0.56

Splicing

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

Other links and lift over

dbSNP: rs12432593; hg19: chr14-34731592;