rs12432593

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000551935.5(EGLN3):​n.60-92740G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 151,832 control chromosomes in the GnomAD database, including 18,954 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 0.50 ( 18954 hom., cov: 31)

Consequence

EGLN3
ENST00000551935.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.555
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.641 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
EGLN3ENST00000551935.5 linkn.60-92740G>T intron_variant Intron 1 of 4 4

Frequencies

GnomAD3 genomes
AF:
0.497
AC:
75365
AN:
151714
Hom.:
18933
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.450
Gnomad AMI
AF:
0.375
Gnomad AMR
AF:
0.581
Gnomad ASJ
AF:
0.496
Gnomad EAS
AF:
0.660
Gnomad SAS
AF:
0.541
Gnomad FIN
AF:
0.521
Gnomad MID
AF:
0.459
Gnomad NFE
AF:
0.487
Gnomad OTH
AF:
0.538
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.497
AC:
75441
AN:
151832
Hom.:
18954
Cov.:
31
AF XY:
0.500
AC XY:
37126
AN XY:
74194
show subpopulations
Gnomad4 AFR
AF:
0.450
Gnomad4 AMR
AF:
0.581
Gnomad4 ASJ
AF:
0.496
Gnomad4 EAS
AF:
0.659
Gnomad4 SAS
AF:
0.542
Gnomad4 FIN
AF:
0.521
Gnomad4 NFE
AF:
0.488
Gnomad4 OTH
AF:
0.543
Alfa
AF:
0.483
Hom.:
2857
Bravo
AF:
0.497
Asia WGS
AF:
0.626
AC:
2179
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
8.1
DANN
Benign
0.69

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs12432593; hg19: chr14-34731592; API