rs1182227189
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_022051.3(EGLN1):c.122_124delACT(p.Tyr41del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00000193 in 1,555,448 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
EGLN1
NM_022051.3 disruptive_inframe_deletion
NM_022051.3 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.48
Publications
1 publications found
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]
EGLN1 Gene-Disease associations (from GenCC):
- erythrocytosis, familial, 3Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)
- autosomal dominant secondary polycythemiaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- hemoglobin, high altitude adaptationInheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
- hereditary pheochromocytoma-paragangliomaInheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_022051.3. Strenght limited to Supporting due to length of the change: 1aa.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_022051.3. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| EGLN1 | NM_022051.3 | MANE Select | c.122_124delACT | p.Tyr41del | disruptive_inframe_deletion | Exon 1 of 5 | NP_071334.1 | ||
| EGLN1 | NM_001377260.1 | c.122_124delACT | p.Tyr41del | disruptive_inframe_deletion | Exon 1 of 4 | NP_001364189.1 | |||
| EGLN1 | NM_001377261.1 | c.122_124delACT | p.Tyr41del | disruptive_inframe_deletion | Exon 1 of 4 | NP_001364190.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| EGLN1 | ENST00000366641.4 | TSL:1 MANE Select | c.122_124delACT | p.Tyr41del | disruptive_inframe_deletion | Exon 1 of 5 | ENSP00000355601.3 | ||
| ENSG00000287856 | ENST00000662216.1 | c.30+40671_30+40673delACT | intron | N/A | ENSP00000499467.1 | ||||
| ENSG00000287856 | ENST00000653908.1 | c.30+40671_30+40673delACT | intron | N/A | ENSP00000499669.1 |
Frequencies
GnomAD3 genomes 0.00000659 AC: 1AN: 151798Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
151798
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000142 AC: 2AN: 1403650Hom.: 0 AF XY: 0.00000287 AC XY: 2AN XY: 697030 show subpopulations
GnomAD4 exome
AF:
AC:
2
AN:
1403650
Hom.:
AF XY:
AC XY:
2
AN XY:
697030
show subpopulations
African (AFR)
AF:
AC:
1
AN:
30248
American (AMR)
AF:
AC:
0
AN:
40088
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
24964
East Asian (EAS)
AF:
AC:
0
AN:
35846
South Asian (SAS)
AF:
AC:
0
AN:
80900
European-Finnish (FIN)
AF:
AC:
0
AN:
36856
Middle Eastern (MID)
AF:
AC:
0
AN:
4054
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1092354
Other (OTH)
AF:
AC:
0
AN:
58340
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.450
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome 0.00000659 AC: 1AN: 151798Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74160 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
151798
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74160
show subpopulations
African (AFR)
AF:
AC:
1
AN:
41376
American (AMR)
AF:
AC:
0
AN:
15260
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3468
East Asian (EAS)
AF:
AC:
0
AN:
5136
South Asian (SAS)
AF:
AC:
0
AN:
4834
European-Finnish (FIN)
AF:
AC:
0
AN:
10528
Middle Eastern (MID)
AF:
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
AC:
0
AN:
67890
Other (OTH)
AF:
AC:
0
AN:
2086
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
ClinVar submissions as Germline
Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
Erythrocytosis, familial, 3 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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