rs3834043
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1BS2
The NM_005957.5(MTHFR):c.-14+128del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00179 in 155,908 control chromosomes in the GnomAD database, including 2 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0018 ( 2 hom., cov: 31)
Exomes 𝑓: 0.0015 ( 0 hom. )
Consequence
MTHFR
NM_005957.5 intron
NM_005957.5 intron
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.03
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 -8 ACMG points.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0018 (273/152006) while in subpopulation NFE AF= 0.00274 (186/67924). AF 95% confidence interval is 0.00242. There are 2 homozygotes in gnomad4. There are 139 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MTHFR | NM_005957.5 | c.-14+128del | intron_variant | ENST00000376590.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MTHFR | ENST00000376590.9 | c.-14+128del | intron_variant | 1 | NM_005957.5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00180 AC: 273AN: 151888Hom.: 2 Cov.: 31
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GnomAD4 exome AF: 0.00154 AC: 6AN: 3902Hom.: 0 Cov.: 0 AF XY: 0.000504 AC XY: 1AN XY: 1984
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GnomAD4 genome ? AF: 0.00180 AC: 273AN: 152006Hom.: 2 Cov.: 31 AF XY: 0.00187 AC XY: 139AN XY: 74322
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ClinVar
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at