14-34006606-G-C

Position:

• chr14-34006606-G-C

Variant summary

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

The ENST00000487915.6(EGLN3):​c.4-75391C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.887 in 152,020 control chromosomes in the GnomAD database, including 59,974 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 0.89 (59974 hom., cov: 29)
• Consequence: EGLN3 ENST00000487915.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330

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]

EGLN3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC102724945	XR_001750942.2	n.484-19444C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGLN3	ENST00000487915.6	c.4-75391C>G		intron_variant		5		ENSP00000451316.1
EGLN3	ENST00000550114.5	n.55+11995C>G		intron_variant		4
EGLN3	ENST00000551935.5	n.298-19444C>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.887 AC: 134746 AN: 151902 Hom.: 59931 Cov.: 29

Gnomad AFR AF: 0.912

Gnomad AMI AF: 0.833

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.886

Gnomad EAS AF: 0.898

Gnomad SAS AF: 0.914

Gnomad FIN AF: 0.919

Gnomad MID AF: 0.863

Gnomad NFE AF: 0.889

Gnomad OTH AF: 0.860

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

GnomAD4 genome AF: 0.887 AC: 134847 AN: 152020 Hom.: 59974 Cov.: 29 AF XY: 0.888 AC XY: 65958 AN XY: 74282

Gnomad4 AFR AF: 0.912

Gnomad4 AMR AF: 0.783

Gnomad4 ASJ AF: 0.886

Gnomad4 EAS AF: 0.898

Gnomad4 SAS AF: 0.915

Gnomad4 FIN AF: 0.919

Gnomad4 NFE AF: 0.889

Gnomad4 OTH AF: 0.859

Alfa AF: 0.897 Hom.: 7145

Bravo AF: 0.875

Asia WGS AF: 0.867 AC: 3015 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.0
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1626390; hg19: chr14-34475812;