1-11801990-C-T

Position:

• chr1-11801990-C-T

Variant summary

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

The NM_005957.5(MTHFR):​c.237-591G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0989 in 150,400 control chromosomes in the GnomAD database, including 795 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 0.099 (795 hom., cov: 31)
• Consequence: MTHFR NM_005957.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.46

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=-0.88).
• 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	UniProt
MTHFR	NM_005957.5	c.237-591G>A		intron_variant		ENST00000376590.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTHFR	ENST00000376590.9	c.237-591G>A		intron_variant		1	NM_005957.5	A1

Frequencies

GnomAD3 genomes AF: 0.0990 AC: 14874 AN: 150306 Hom.: 798 Cov.: 31

Gnomad AFR AF: 0.0933

Gnomad AMI AF: 0.0475

Gnomad AMR AF: 0.0677

Gnomad ASJ AF: 0.0324

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0390

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.0832

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

GnomAD4 genome AF: 0.0989 AC: 14870 AN: 150400 Hom.: 795 Cov.: 31 AF XY: 0.0994 AC XY: 7288 AN XY: 73292

Gnomad4 AFR AF: 0.0931

Gnomad4 AMR AF: 0.0672

Gnomad4 ASJ AF: 0.0324

Gnomad4 EAS AF: 0.131

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.0833

Alfa AF: 0.0948 Hom.: 738

Bravo AF: 0.0935

Asia WGS AF: 0.131 AC: 456 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.022
DANN	Benign	0.77

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: rs17037396; hg19: chr1-11862047;