chr14-34375170-T-C

Variant names:

• chr14-34375170-T-C
• rs1958589
• ENST00000551935.5:n.59+87546A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000551935.5(EGLN3):​n.59+87546A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,154 control chromosomes in the GnomAD database, including 4,062 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 0.21 (4062 hom., cov: 32)
• Consequence: EGLN3 ENST00000551935.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.866
• Publications: 11 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGLN3	ENST00000551935.5	n.59+87546A>G		intron_variant	Intron 1 of 4	4

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31548 AN: 152036 Hom.: 4053 Cov.: 32

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.0608

Gnomad EAS AF: 0.0962

Gnomad SAS AF: 0.0956

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.208 AC: 31594 AN: 152154 Hom.: 4062 Cov.: 32 AF XY: 0.211 AC XY: 15676 AN XY: 74400

African (AFR) AF: 0.329 AC: 13666 AN: 41482

American (AMR) AF: 0.316 AC: 4831 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0608 AC: 211 AN: 3468

East Asian (EAS) AF: 0.0952 AC: 494 AN: 5188

South Asian (SAS) AF: 0.0965 AC: 465 AN: 4820

European-Finnish (FIN) AF: 0.232 AC: 2460 AN: 10590

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 9009 AN: 68006

Other (OTH) AF: 0.161 AC: 340 AN: 2110

Alfa AF: 0.154 Hom.: 4558

Bravo AF: 0.219

Asia WGS AF: 0.106 AC: 370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	6.0
DANN	Benign	0.74
PhyloP100		0.87

Splicing

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

Other links and lift over

dbSNP: rs1958589; hg19: chr14-34844376;