rs768557500
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_022051.3(EGLN1):c.419C>T(p.Ala140Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000124 in 1,454,392 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. A140A) has been classified as Likely benign.
Frequency
Consequence
NM_022051.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EGLN1 | NM_022051.3 | c.419C>T | p.Ala140Val | missense_variant | 1/5 | ENST00000366641.4 | |
EGLN1 | NM_001377260.1 | c.419C>T | p.Ala140Val | missense_variant | 1/4 | ||
EGLN1 | NM_001377261.1 | c.419C>T | p.Ala140Val | missense_variant | 1/4 | ||
EGLN1 | XM_024447734.2 | c.419C>T | p.Ala140Val | missense_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EGLN1 | ENST00000366641.4 | c.419C>T | p.Ala140Val | missense_variant | 1/5 | 1 | NM_022051.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000923 AC: 14AN: 151692Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000102 AC: 6AN: 59082Hom.: 0 AF XY: 0.000197 AC XY: 6AN XY: 30468
GnomAD4 exome AF: 0.000128 AC: 167AN: 1302700Hom.: 1 Cov.: 31 AF XY: 0.000137 AC XY: 87AN XY: 633954
GnomAD4 genome ? AF: 0.0000923 AC: 14AN: 151692Hom.: 0 Cov.: 32 AF XY: 0.0000810 AC XY: 6AN XY: 74082
ClinVar
Submissions by phenotype
Erythrocytosis, familial, 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 04, 2023 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 407204). This variant has not been reported in the literature in individuals affected with EGLN1-related conditions. This variant is present in population databases (rs768557500, gnomAD 0.02%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 140 of the EGLN1 protein (p.Ala140Val). - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 25, 2022 | This 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at