rs4981220

Variant names:

• chr14-34130140-G-A
• rs4981220
• ENST00000487915.6:c.-79-37738C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

LOC102724945 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LOC102724945	XR_001750942.2	n.227-2996C>T		intron_variant	Intron 2 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGLN3	ENST00000487915.6	c.-79-37738C>T		intron_variant	Intron 3 of 5	5		ENSP00000451316.1
EGLN3	ENST00000464521.6	n.178-2996C>T		intron_variant	Intron 2 of 3	5
EGLN3	ENST00000546681.5	n.213-2996C>T		intron_variant	Intron 2 of 3	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

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 7 AN: 14

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.215 AC: 8930 AN: 41472

American (AMR) AF: 0.345 AC: 5273 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 982 AN: 3466

East Asian (EAS) AF: 0.421 AC: 2170 AN: 5152

South Asian (SAS) AF: 0.280 AC: 1351 AN: 4818

European-Finnish (FIN) AF: 0.330 AC: 3479 AN: 10544

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.286 AC: 19447 AN: 67946

Other (OTH) AF: 0.307 AC: 647 AN: 2108

Alfa AF: 0.287 Hom.: 12230

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
PhyloP100		-0.43

Splicing

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

Other links and lift over

dbSNP: rs4981220; hg19: chr14-34599346;