1-11797654-T-C

Position:

• chr1-11797654-T-C

Variant summary

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

The ENST00000376590.9(MTHFR):​c.587-1255A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0669 in 152,160 control chromosomes in the GnomAD database, including 387 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 0.067 (387 hom., cov: 32)
• Consequence: MTHFR ENST00000376590.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.128

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 = 0.0903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTHFR	NM_005957.5	c.587-1255A>G		intron_variant		ENST00000376590.9	NP_005948.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTHFR	ENST00000376590.9	c.587-1255A>G		intron_variant		1	NM_005957.5	ENSP00000365775	A1

Frequencies

GnomAD3 genomes AF: 0.0670 AC: 10182 AN: 152042 Hom.: 387 Cov.: 32

Gnomad AFR AF: 0.0583

Gnomad AMI AF: 0.0945

Gnomad AMR AF: 0.0560

Gnomad ASJ AF: 0.0490

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0979

Gnomad FIN AF: 0.0392

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0818

Gnomad OTH AF: 0.0832

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

GnomAD4 genome AF: 0.0669 AC: 10186 AN: 152160 Hom.: 387 Cov.: 32 AF XY: 0.0661 AC XY: 4913 AN XY: 74380

Gnomad4 AFR AF: 0.0583

Gnomad4 AMR AF: 0.0560

Gnomad4 ASJ AF: 0.0490

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0976

Gnomad4 FIN AF: 0.0392

Gnomad4 NFE AF: 0.0818

Gnomad4 OTH AF: 0.0823

Alfa AF: 0.0796 Hom.: 749

Bravo AF: 0.0680

Asia WGS AF: 0.0400 AC: 137 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	3.4
DANN	Benign	0.58

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: rs1572151; hg19: chr1-11857711;