1-11805759-GC-GCC

Position:

• chr1-11805759-GC-GCC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_005957.5(MTHFR):​c.-14+128dupG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0978 in 155,862 control chromosomes in the GnomAD database, including 795 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.099 (788 hom., cov: 31)
  • Exomes 𝑓: 0.071 (7 hom.)
• Consequence: MTHFR NM_005957.5 intron
• 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]

MTHFR (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTHFR	NM_005957.5	c.-14+128dupG		intron_variant		ENST00000376590.9	NP_005948.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTHFR	ENST00000376590.9	c.-14+128dupG		intron_variant		1	NM_005957.5	ENSP00000365775.3

Frequencies

GnomAD3 genomes AF: 0.0986 AC: 14976 AN: 151864 Hom.: 791 Cov.: 31

Gnomad AFR AF: 0.0947

Gnomad AMI AF: 0.0484

Gnomad AMR AF: 0.0682

Gnomad ASJ AF: 0.0314

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.0414

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0831

GnomAD4 exome AF: 0.0711 AC: 276 AN: 3880 Hom.: 7 Cov.: 0 AF XY: 0.0773 AC XY: 153 AN XY: 1980

Gnomad4 AFR exome AF: 0.0783

Gnomad4 AMR exome AF: 0.0250

Gnomad4 ASJ exome AF: 0.00935

Gnomad4 EAS exome AF: 0.0708

Gnomad4 SAS exome AF: 0.0928

Gnomad4 FIN exome AF: 0.0658

Gnomad4 NFE exome AF: 0.0776

Gnomad4 OTH exome AF: 0.0588

GnomAD4 genome AF: 0.0985 AC: 14973 AN: 151982 Hom.: 788 Cov.: 31 AF XY: 0.0993 AC XY: 7381 AN XY: 74306

Gnomad4 AFR AF: 0.0945

Gnomad4 AMR AF: 0.0678

Gnomad4 ASJ AF: 0.0314

Gnomad4 EAS AF: 0.123

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.0832

Bravo AF: 0.0922

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3834043; hg19: chr1-11865816;