rs11625217

Positions:

• chr14-34259025-G-A

Variant summary

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

The ENST00000551935.5(EGLN3):​n.60-89379C>T 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 0.548 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, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.393

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGLN3	ENST00000551935.5	n.60-89379C>T		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.621

Gnomad4 AMR AF: 0.604

Gnomad4 ASJ AF: 0.497

Gnomad4 EAS AF: 0.664

Gnomad4 SAS AF: 0.545

Gnomad4 FIN AF: 0.523

Gnomad4 NFE AF: 0.489

Gnomad4 OTH AF: 0.577

Alfa AF: 0.524 Hom.: 9580

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11625217; hg19: chr14-34728231;