rs17037397

Positions:

• chr1-11802106-C-A

Variant summary

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

The NM_005957.5(MTHFR):​c.237-707G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0437 in 152,216 control chromosomes in the GnomAD database, including 215 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 0.044 (215 hom., cov: 32)
• Consequence: MTHFR NM_005957.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.435

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTHFR	NM_005957.5	c.237-707G>T		intron_variant		ENST00000376590.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTHFR	ENST00000376590.9	c.237-707G>T		intron_variant		1	NM_005957.5	A1

Frequencies

GnomAD3 genomes AF: 0.0437 AC: 6648 AN: 152098 Hom.: 216 Cov.: 32

Gnomad AFR AF: 0.0312

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0434

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0159

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0469

Gnomad OTH AF: 0.0441

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0437 AC: 6645 AN: 152216 Hom.: 215 Cov.: 32 AF XY: 0.0433 AC XY: 3224 AN XY: 74410

Gnomad4 AFR AF: 0.0311

Gnomad4 AMR AF: 0.0431

Gnomad4 ASJ AF: 0.0161

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.0159

Gnomad4 NFE AF: 0.0469

Gnomad4 OTH AF: 0.0445

Alfa AF: 0.0443 Hom.: 186

Bravo AF: 0.0432

Asia WGS AF: 0.110 AC: 380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.7
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs17037397; hg19: chr1-11862163;