rs11625217

Variant names:

• chr14-34259025-G-A
• rs11625217
• ENST00000551935.5:n.60-89379C>T

Variant summary

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

The ENST00000551935.5(EGLN3):​n.60-89379C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 151,846 control chromosomes in the GnomAD database, including 23,058 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 0.55 (23058 hom., cov: 30)
• Consequence: EGLN3 ENST00000551935.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.393
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.646 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.60-89379C>T		intron_variant	Intron 1 of 4	4

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83043 AN: 151728 Hom.: 23020 Cov.: 30

Gnomad AFR AF: 0.621

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.573

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

GnomAD4 genome AF: 0.548 AC: 83137 AN: 151846 Hom.: 23058 Cov.: 30 AF XY: 0.549 AC XY: 40721 AN XY: 74182

African (AFR) AF: 0.621 AC: 25715 AN: 41398

American (AMR) AF: 0.604 AC: 9233 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1722 AN: 3466

East Asian (EAS) AF: 0.664 AC: 3402 AN: 5122

South Asian (SAS) AF: 0.545 AC: 2614 AN: 4794

European-Finnish (FIN) AF: 0.523 AC: 5518 AN: 10548

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.489 AC: 33234 AN: 67936

Other (OTH) AF: 0.577 AC: 1215 AN: 2104

Alfa AF: 0.525 Hom.: 11341

Bravo AF: 0.554

Asia WGS AF: 0.640 AC: 2230 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.2
DANN	Benign	0.74
PhyloP100		0.39

Splicing

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

Other links and lift over

dbSNP: rs11625217; hg19: chr14-34728231;