rs2027338

Positions:

• chr14-34117457-C-T

Variant summary

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

The ENST00000487915.6(EGLN3):​c.-79-25055G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 152,042 control chromosomes in the GnomAD database, including 24,499 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 0.57 (24499 hom., cov: 32)
• Consequence: EGLN3 ENST00000487915.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC102724945	XR_001750942.2	n.401+8796G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGLN3	ENST00000487915.6	c.-79-25055G>A		intron_variant		5		ENSP00000451316.1
EGLN3	ENST00000546681.5	n.328+9572G>A		intron_variant		5
EGLN3	ENST00000548285.5	n.449+8796G>A		intron_variant		3
EGLN3	ENST00000551935.5	n.216-25055G>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86246 AN: 151924 Hom.: 24485 Cov.: 32

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.565

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

GnomAD4 genome AF: 0.568 AC: 86311 AN: 152042 Hom.: 24499 Cov.: 32 AF XY: 0.568 AC XY: 42223 AN XY: 74318

Gnomad4 AFR AF: 0.559

Gnomad4 AMR AF: 0.649

Gnomad4 ASJ AF: 0.588

Gnomad4 EAS AF: 0.465

Gnomad4 SAS AF: 0.584

Gnomad4 FIN AF: 0.563

Gnomad4 NFE AF: 0.561

Gnomad4 OTH AF: 0.561

Alfa AF: 0.571 Hom.: 3077

Bravo AF: 0.573

Asia WGS AF: 0.499 AC: 1736 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.52

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2027338; hg19: chr14-34586663;