rs781566823

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_022051.3(EGLN1):​c.405C>T​(p.Gly135Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000228 in 1,359,254 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. G135G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

EGLN1
NM_022051.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.00500
Variant links:
Genes affected
EGLN1 (HGNC:1232): (egl-9 family hypoxia inducible factor 1) The protein encoded by this gene catalyzes the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. HIF is a transcriptional complex that plays a central role in mammalian oxygen homeostasis. This protein functions as a cellular oxygen sensor, and under normal oxygen concentration, modification by prolyl hydroxylation is a key regulatory event that targets HIF subunits for proteasomal destruction via the von Hippel-Lindau ubiquitylation complex. Mutations in this gene are associated with erythrocytosis familial type 3 (ECYT3). [provided by RefSeq, Nov 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 1-231421484-G-A is Benign according to our data. Variant chr1-231421484-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 465824.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.005 with no splicing effect.
BS2
High AC in GnomAdExome4 at 27 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EGLN1NM_022051.3 linkc.405C>T p.Gly135Gly synonymous_variant Exon 1 of 5 ENST00000366641.4 NP_071334.1 Q9GZT9-1R4SCQ0
EGLN1NM_001377260.1 linkc.405C>T p.Gly135Gly synonymous_variant Exon 1 of 4 NP_001364189.1
EGLN1NM_001377261.1 linkc.405C>T p.Gly135Gly synonymous_variant Exon 1 of 4 NP_001364190.1
EGLN1XM_024447734.2 linkc.405C>T p.Gly135Gly synonymous_variant Exon 1 of 3 XP_024303502.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EGLN1ENST00000366641.4 linkc.405C>T p.Gly135Gly synonymous_variant Exon 1 of 5 1 NM_022051.3 ENSP00000355601.3 Q9GZT9-1
ENSG00000287856ENST00000662216.1 linkc.30+40954C>T intron_variant Intron 3 of 6 ENSP00000499467.1 A0A590UJK7
ENSG00000287856ENST00000653908.1 linkc.30+40954C>T intron_variant Intron 2 of 4 ENSP00000499669.1 A0A590UK27
ENSG00000287856ENST00000653198.1 linkn.433+40988C>T intron_variant Intron 4 of 7

Frequencies

GnomAD3 genomes
AF:
0.0000198
AC:
3
AN:
151714
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000442
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000117
AC:
2
AN:
17036
Hom.:
0
AF XY:
0.000114
AC XY:
1
AN XY:
8806
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000479
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000224
AC:
27
AN:
1207432
Hom.:
0
Cov.:
31
AF XY:
0.0000206
AC XY:
12
AN XY:
582276
show subpopulations
Gnomad4 AFR exome
AF:
0.0000426
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000242
Gnomad4 OTH exome
AF:
0.0000407
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
151822
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74204
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000442
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000142
Hom.:
0
Bravo
AF:
0.0000113

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsApr 26, 2022This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Erythrocytosis, familial, 3 Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpAug 28, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
7.7
DANN
Benign
0.90
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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: rs781566823; hg19: chr1-231557230; COSMIC: COSV64149020; COSMIC: COSV64149020; API