1-231364607-A-ATT
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2
The NM_022051.3(EGLN1):c.*1802_*1803dupAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00039 ( 0 hom., cov: 0)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
EGLN1
NM_022051.3 3_prime_UTR
NM_022051.3 3_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.160
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000395 (60/152016) while in subpopulation AFR AF= 0.00138 (57/41406). AF 95% confidence interval is 0.00109. There are 0 homozygotes in gnomad4. There are 35 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
High AC in GnomAd4 at 60 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EGLN1 | NM_022051.3 | c.*1802_*1803dupAA | 3_prime_UTR_variant | Exon 5 of 5 | ENST00000366641.4 | NP_071334.1 | ||
EGLN1 | NM_001377260.1 | c.*1863_*1864dupAA | 3_prime_UTR_variant | Exon 4 of 4 | NP_001364189.1 | |||
EGLN1 | NM_001377261.1 | c.*1908_*1909dupAA | 3_prime_UTR_variant | Exon 4 of 4 | NP_001364190.1 | |||
LOC107985360 | XR_001738520.3 | n.4098+3226_4098+3227dupTT | intron_variant | Intron 1 of 1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
EGLN1 | ENST00000366641 | c.*1802_*1803dupAA | 3_prime_UTR_variant | Exon 5 of 5 | 1 | NM_022051.3 | ENSP00000355601.3 | |||
EGLN1 | ENST00000667629 | c.*1908_*1909dupAA | 3_prime_UTR_variant | Exon 4 of 4 | ENSP00000499629.1 | |||||
ENSG00000287856 | ENST00000653908 | c.*1908_*1909dupAA | 3_prime_UTR_variant | Exon 5 of 5 | ENSP00000499669.1 | |||||
ENSG00000287856 | ENST00000653198.1 | n.2625_2626dupAA | non_coding_transcript_exon_variant | Exon 8 of 8 |
Frequencies
GnomAD3 genomes AF: 0.000388 AC: 59AN: 151900Hom.: 0 Cov.: 0
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GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 2Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 2
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GnomAD4 genome AF: 0.000395 AC: 60AN: 152016Hom.: 0 Cov.: 0 AF XY: 0.000471 AC XY: 35AN XY: 74298
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Familial erythrocytosis Uncertain:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at