rs13306561

Positions:

• chr1-11805747-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005957.5(MTHFR):​c.-14+141T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 154,544 control chromosomes in the GnomAD database, including 2,652 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 0.18 (2631 hom., cov: 33)
  • Exomes 𝑓: 0.12 (21 hom.)
• Consequence: MTHFR NM_005957.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTHFR	NM_005957.5	c.-14+141T>C		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+141T>C		intron_variant		1	NM_005957.5	ENSP00000365775.3

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27082 AN: 152076 Hom.: 2624 Cov.: 33

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.0846

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.0935

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.155

GnomAD4 exome AF: 0.120 AC: 283 AN: 2350 Hom.: 21 Cov.: 0 AF XY: 0.125 AC XY: 155 AN XY: 1236

Gnomad4 AFR exome AF: 0.200

Gnomad4 AMR exome AF: 0.105

Gnomad4 ASJ exome AF: 0.0574

Gnomad4 EAS exome AF: 0.0648

Gnomad4 SAS exome AF: 0.144

Gnomad4 FIN exome AF: 0.0682

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.127

GnomAD4 genome AF: 0.178 AC: 27119 AN: 152194 Hom.: 2631 Cov.: 33 AF XY: 0.178 AC XY: 13274 AN XY: 74408

Gnomad4 AFR AF: 0.252

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.0935

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.158

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.158

Alfa AF: 0.154 Hom.: 1887

Bravo AF: 0.177

Asia WGS AF: 0.171 AC: 594 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.2
DANN	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13306561; hg19: chr1-11865804;