rs4981220

Positions:

• chr14-34130140-G-A

Variant summary

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

The ENST00000487915.6(EGLN3):​c.-79-37738C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 152,022 control chromosomes in the GnomAD database, including 6,190 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 0.28 (6189 hom., cov: 32)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: EGLN3 ENST00000487915.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.426

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC102724945	XR_001750942.2	n.227-2996C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGLN3	ENST00000487915.6	c.-79-37738C>T		intron_variant		5		ENSP00000451316.1
EGLN3	ENST00000464521.6	n.178-2996C>T		intron_variant		5
EGLN3	ENST00000546681.5	n.213-2996C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42603 AN: 151886 Hom.: 6176 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.301

GnomAD4 exome AF: 0.500 AC: 9 AN: 18 Hom.: 1 AF XY: 0.583 AC XY: 7 AN XY: 12

Gnomad4 AFR exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.281 AC: 42659 AN: 152004 Hom.: 6189 Cov.: 32 AF XY: 0.285 AC XY: 21154 AN XY: 74272

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.345

Gnomad4 ASJ AF: 0.283

Gnomad4 EAS AF: 0.421

Gnomad4 SAS AF: 0.280

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.286

Gnomad4 OTH AF: 0.307

Alfa AF: 0.287 Hom.: 8842

Bravo AF: 0.283

Asia WGS AF: 0.377 AC: 1310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.91
DANN	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4981220; hg19: chr14-34599346;