14-34275220-T-C

Position:

• chr14-34275220-T-C

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, non coding transcript 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, non_coding_transcript
• 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/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGLN3	ENST00000551935.5	n.60-105574A>G		intron_variant, non_coding_transcript_variant		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;