rs143175221
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1
The NM_000410.4(HFE):āc.884T>Cā(p.Val295Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000417 in 1,614,014 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000410.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HFE | NM_000410.4 | c.884T>C | p.Val295Ala | missense_variant | 4/6 | ENST00000357618.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HFE | ENST00000357618.10 | c.884T>C | p.Val295Ala | missense_variant | 4/6 | 1 | NM_000410.4 | P3 |
Frequencies
GnomAD3 genomes AF: 0.000605 AC: 92AN: 152186Hom.: 1 Cov.: 31
GnomAD3 exomes AF: 0.000841 AC: 211AN: 251032Hom.: 0 AF XY: 0.000899 AC XY: 122AN XY: 135756
GnomAD4 exome AF: 0.000397 AC: 581AN: 1461710Hom.: 1 Cov.: 34 AF XY: 0.000459 AC XY: 334AN XY: 727164
GnomAD4 genome AF: 0.000604 AC: 92AN: 152304Hom.: 1 Cov.: 31 AF XY: 0.000752 AC XY: 56AN XY: 74470
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 10, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2023 | HFE: BP4 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 09, 2020 | This variant is associated with the following publications: (PMID: 19787796, 22624560, 24872867, 15046077, 12542741, 26456104) - |
Hemochromatosis type 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Hereditary hemochromatosis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at