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

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.160
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 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
EGLN1NM_022051.3 linkc.*1802_*1803dupAA 3_prime_UTR_variant Exon 5 of 5 ENST00000366641.4 NP_071334.1 Q9GZT9-1R4SCQ0
EGLN1NM_001377260.1 linkc.*1863_*1864dupAA 3_prime_UTR_variant Exon 4 of 4 NP_001364189.1
EGLN1NM_001377261.1 linkc.*1908_*1909dupAA 3_prime_UTR_variant Exon 4 of 4 NP_001364190.1
LOC107985360XR_001738520.3 linkn.4098+3226_4098+3227dupTT intron_variant Intron 1 of 1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EGLN1ENST00000366641 linkc.*1802_*1803dupAA 3_prime_UTR_variant Exon 5 of 5 1 NM_022051.3 ENSP00000355601.3 Q9GZT9-1
EGLN1ENST00000667629 linkc.*1908_*1909dupAA 3_prime_UTR_variant Exon 4 of 4 ENSP00000499629.1 A0A590UJZ0
ENSG00000287856ENST00000653908 linkc.*1908_*1909dupAA 3_prime_UTR_variant Exon 5 of 5 ENSP00000499669.1 A0A590UK27
ENSG00000287856ENST00000653198.1 linkn.2625_2626dupAA non_coding_transcript_exon_variant Exon 8 of 8

Frequencies

GnomAD3 genomes
AF:
0.000388
AC:
59
AN:
151900
Hom.:
0
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.00136
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
2
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
2
Gnomad4 FIN exome
AF:
0.00
GnomAD4 genome
AF:
0.000395
AC:
60
AN:
152016
Hom.:
0
Cov.:
0
AF XY:
0.000471
AC XY:
35
AN XY:
74298
show subpopulations
Gnomad4 AFR
AF:
0.00138
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00

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

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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: rs541569859; hg19: chr1-231500353; API