rs1032015

Positions:

• chr14-33931898-T-C

Variant summary

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

The ENST00000250457.9(EGLN3):​c.358-683A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 152,144 control chromosomes in the GnomAD database, including 9,938 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 0.35 (9938 hom., cov: 33)
• Consequence: EGLN3 ENST00000250457.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.289

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGLN3	NM_022073.4	c.358-683A>G		intron_variant		ENST00000250457.9	NP_071356.1
EGLN3	NM_001308103.2	c.76-683A>G		intron_variant			NP_001295032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGLN3	ENST00000250457.9	c.358-683A>G		intron_variant		1	NM_022073.4	ENSP00000250457	P1
EGLN3	ENST00000553215.5	c.76-683A>G		intron_variant		1		ENSP00000447470
EGLN3	ENST00000487915.6	c.4-683A>G		intron_variant		5		ENSP00000451316

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52488 AN: 152026 Hom.: 9936 Cov.: 33

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.336

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

GnomAD4 genome AF: 0.345 AC: 52494 AN: 152144 Hom.: 9938 Cov.: 33 AF XY: 0.336 AC XY: 25023 AN XY: 74364

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.269

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.285

Gnomad4 SAS AF: 0.258

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.441

Gnomad4 OTH AF: 0.339

Alfa AF: 0.414 Hom.: 27215

Bravo AF: 0.332

Asia WGS AF: 0.300 AC: 1044 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	4.6
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1032015; hg19: chr14-34401104;