14-34275220-T-C

Variant names:

• chr14-34275220-T-C
• rs4624074
• ENST00000551935.5:n.60-105574A>G

Variant summary

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

The ENST00000551935.5(EGLN3):​n.60-105574A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 151,956 control chromosomes in the GnomAD database, including 12,710 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 0.39 (12710 hom., cov: 32)
• Consequence: EGLN3 ENST00000551935.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94

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=-0.54).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.624 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.60-105574A>G		intron_variant	Intron 1 of 4	4

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59737 AN: 151838 Hom.: 12704 Cov.: 32

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.439

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

GnomAD4 genome AF: 0.393 AC: 59758 AN: 151956 Hom.: 12710 Cov.: 32 AF XY: 0.394 AC XY: 29235 AN XY: 74254

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.370

Gnomad4 ASJ AF: 0.457

Gnomad4 EAS AF: 0.642

Gnomad4 SAS AF: 0.435

Gnomad4 FIN AF: 0.465

Gnomad4 NFE AF: 0.460

Gnomad4 OTH AF: 0.446

Alfa AF: 0.449 Hom.: 32198

Bravo AF: 0.377

Asia WGS AF: 0.535 AC: 1863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Benign	0.84

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4624074; hg19: chr14-34744426;