14-34275220-T-C

Variant names:

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

Variant summary

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

The ENST00000551935.5(EGLN3):​n.60-105574A>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
• Publications: 7 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=-0.54).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000551935.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGLN3	ENST00000551935.5	TSL:4	n.60-105574A>G		intron	N/A

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

African (AFR) AF: 0.231 AC: 9591 AN: 41460

American (AMR) AF: 0.370 AC: 5638 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 1588 AN: 3472

East Asian (EAS) AF: 0.642 AC: 3305 AN: 5144

South Asian (SAS) AF: 0.435 AC: 2092 AN: 4810

European-Finnish (FIN) AF: 0.465 AC: 4900 AN: 10534

Middle Eastern (MID) AF: 0.387 AC: 113 AN: 292

European-Non Finnish (NFE) AF: 0.460 AC: 31236 AN: 67966

Other (OTH) AF: 0.446 AC: 941 AN: 2112

Alfa AF: 0.434 Hom.: 46644

Bravo AF: 0.377

Asia WGS AF: 0.535 AC: 1863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Benign	0.84
PhyloP100		1.9

Splicing

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

Other links and lift over

dbSNP: rs4624074; hg19: chr14-34744426;