rs1680692

Positions:

• chr14-33942159-A-G

Variant summary

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

The NM_022073.4(EGLN3):​c.357+8237T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 152,026 control chromosomes in the GnomAD database, including 8,541 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 0.33 (8541 hom., cov: 31)
• Consequence: EGLN3 NM_022073.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.871

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGLN3	NM_022073.4	c.357+8237T>C		intron_variant		ENST00000250457.9
EGLN3	NM_001308103.2	c.75+8519T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGLN3	ENST00000250457.9	c.357+8237T>C		intron_variant		1	NM_022073.4	P1
EGLN3	ENST00000553215.5	c.75+8519T>C		intron_variant		1
EGLN3	ENST00000487915.6	c.4-10944T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50407 AN: 151906 Hom.: 8536 Cov.: 31

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.332 AC: 50445 AN: 152026 Hom.: 8541 Cov.: 31 AF XY: 0.325 AC XY: 24124 AN XY: 74290

Gnomad4 AFR AF: 0.328

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.283

Gnomad4 EAS AF: 0.248

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.370

Gnomad4 OTH AF: 0.308

Alfa AF: 0.341 Hom.: 1575

Bravo AF: 0.324

Asia WGS AF: 0.255 AC: 888 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.5
DANN	Benign	0.82

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: rs1680692; hg19: chr14-34411365;