chr1-11792354-C-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2
The NM_005957.5(MTHFR):c.1556G>T(p.Arg519Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000448 in 1,614,112 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R519C) has been classified as Likely benign.
Frequency
Consequence
NM_005957.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00112 AC: 170AN: 152202Hom.: 4 Cov.: 33
GnomAD3 exomes AF: 0.000537 AC: 135AN: 251358Hom.: 1 AF XY: 0.000523 AC XY: 71AN XY: 135866
GnomAD4 exome AF: 0.000378 AC: 553AN: 1461792Hom.: 3 Cov.: 31 AF XY: 0.000378 AC XY: 275AN XY: 727200
GnomAD4 genome AF: 0.00112 AC: 170AN: 152320Hom.: 4 Cov.: 33 AF XY: 0.00109 AC XY: 81AN XY: 74498
ClinVar
Submissions by phenotype
Homocystinuria due to methylene tetrahydrofolate reductase deficiency Uncertain:1Benign:2
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not provided Uncertain:2
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Schizophrenia;C1856061:Homocystinuria due to methylene tetrahydrofolate reductase deficiency;C1866558:Neural tube defects, folate-sensitive;C3160733:Thrombophilia due to thrombin defect Uncertain:1
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MTHFR-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at