rs17421462

chr1-11796790-G-Achr1-11796790-G-T

Variant summary

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

The NM_005957.5(MTHFR):c.587-391C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0643 in 152,292 control chromosomes in the GnomAD database, including 354 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 0.064 (354 hom., cov: 31)
• Consequence: MTHFR NM_005957.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0130

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTHFR	NM_005957.5	c.587-391C>T		intron_variant		ENST00000376590.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTHFR	ENST00000376590.9	c.587-391C>T		intron_variant		1	NM_005957.5	A1

Frequencies

GnomAD3 genomes AF: 0.0643 AC: 9787 AN: 152174 Hom.: 354 Cov.: 31

Gnomad AFR AF: 0.0569

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.0554

Gnomad ASJ AF: 0.0490

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0987

Gnomad FIN AF: 0.0318

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0780

Gnomad OTH AF: 0.0819

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

GnomAD4 genome AF: 0.0643 AC: 9789 AN: 152292 Hom.: 354 Cov.: 31 AF XY: 0.0633 AC XY: 4712 AN XY: 74458

Gnomad4 AFR AF: 0.0569

Gnomad4 AMR AF: 0.0553

Gnomad4 ASJ AF: 0.0490

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0984

Gnomad4 FIN AF: 0.0318

Gnomad4 NFE AF: 0.0780

Gnomad4 OTH AF: 0.0810

Alfa AF: 0.0573 Hom.: 101

Bravo AF: 0.0659

Asia WGS AF: 0.0380 AC: 131 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	3.8
Dann	Benign	0.42

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: rs17421462; hg19: chr1-11856847;