rs17037390
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_005957.5(MTHFR):c.475+375C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 395,534 control chromosomes in the GnomAD database, including 5,572 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.17 ( 2454 hom., cov: 32)
Exomes 𝑓: 0.16 ( 3118 hom. )
Consequence
MTHFR
NM_005957.5 intron
NM_005957.5 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.246
Genes affected
MTHFR (HGNC:7436): (methylenetetrahydrofolate reductase) The protein encoded by this gene catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine. Genetic variation in this gene influences susceptibility to occlusive vascular disease, neural tube defects, colon cancer and acute leukemia, and mutations in this gene are associated with methylenetetrahydrofolate reductase deficiency.[provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MTHFR | NM_005957.5 | c.475+375C>T | intron_variant | ENST00000376590.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MTHFR | ENST00000376590.9 | c.475+375C>T | intron_variant | 1 | NM_005957.5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.173 AC: 26326AN: 151988Hom.: 2450 Cov.: 32
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GnomAD4 exome AF: 0.156 AC: 37930AN: 243428Hom.: 3118 Cov.: 0 AF XY: 0.158 AC XY: 20652AN XY: 131106
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GnomAD4 genome ? AF: 0.173 AC: 26352AN: 152106Hom.: 2454 Cov.: 32 AF XY: 0.174 AC XY: 12910AN XY: 74356
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ClinVar
Not reported inComputational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at