14-34011308-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000487915.6(EGLN3):​c.4-80093G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,214 control chromosomes in the GnomAD database, including 1,572 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 0.13 ( 1572 hom., cov: 33)

Consequence

EGLN3
ENST00000487915.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.720

Publications

6 publications found
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 was made for transcript

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 = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LOC102724945XR_001750942.2 linkn.484-24146G>A intron_variant Intron 5 of 8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EGLN3ENST00000487915.6 linkc.4-80093G>A intron_variant Intron 4 of 5 5 ENSP00000451316.1 G3V3M1
EGLN3ENST00000550114.5 linkn.55+7293G>A intron_variant Intron 1 of 2 4
EGLN3ENST00000551935.5 linkn.298-24146G>A intron_variant Intron 3 of 4 4

Frequencies

GnomAD3 genomes
AF:
0.132
AC:
20056
AN:
152094
Hom.:
1572
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0598
Gnomad AMI
AF:
0.202
Gnomad AMR
AF:
0.0882
Gnomad ASJ
AF:
0.143
Gnomad EAS
AF:
0.300
Gnomad SAS
AF:
0.151
Gnomad FIN
AF:
0.148
Gnomad MID
AF:
0.0918
Gnomad NFE
AF:
0.167
Gnomad OTH
AF:
0.137
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.132
AC:
20060
AN:
152214
Hom.:
1572
Cov.:
33
AF XY:
0.133
AC XY:
9870
AN XY:
74418
show subpopulations
African (AFR)
AF:
0.0597
AC:
2479
AN:
41544
American (AMR)
AF:
0.0881
AC:
1347
AN:
15298
Ashkenazi Jewish (ASJ)
AF:
0.143
AC:
495
AN:
3464
East Asian (EAS)
AF:
0.301
AC:
1550
AN:
5152
South Asian (SAS)
AF:
0.152
AC:
732
AN:
4830
European-Finnish (FIN)
AF:
0.148
AC:
1568
AN:
10600
Middle Eastern (MID)
AF:
0.0952
AC:
28
AN:
294
European-Non Finnish (NFE)
AF:
0.167
AC:
11387
AN:
68010
Other (OTH)
AF:
0.137
AC:
290
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
897
1793
2690
3586
4483
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
232
464
696
928
1160
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.146
Hom.:
3045
Bravo
AF:
0.124
Asia WGS
AF:
0.204
AC:
709
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
7.6
DANN
Benign
0.44
PhyloP100
0.72

Splicing

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

Publications

Other links and lift over

dbSNP: rs974673; hg19: chr14-34480514; API