rs6541003

chr1-11795810-G-Achr1-11795810-G-C

Variant summary

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

The NM_005957.5(MTHFR):c.780+396C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 151,982 control chromosomes in the GnomAD database, including 25,324 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 0.57 (25324 hom., cov: 32)
• Consequence: MTHFR NM_005957.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.685

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTHFR	NM_005957.5	c.780+396C>T		intron_variant		ENST00000376590.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTHFR	ENST00000376590.9	c.780+396C>T		intron_variant		1	NM_005957.5	A1

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86320 AN: 151864 Hom.: 25306 Cov.: 32

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.614

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.639

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.568

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

GnomAD4 genome AF: 0.568 AC: 86383 AN: 151982 Hom.: 25324 Cov.: 32 AF XY: 0.571 AC XY: 42395 AN XY: 74268

Gnomad4 AFR AF: 0.440

Gnomad4 AMR AF: 0.689

Gnomad4 ASJ AF: 0.634

Gnomad4 EAS AF: 0.779

Gnomad4 SAS AF: 0.493

Gnomad4 FIN AF: 0.639

Gnomad4 NFE AF: 0.594

Gnomad4 OTH AF: 0.567

Alfa AF: 0.593 Hom.: 38470

Bravo AF: 0.570

Asia WGS AF: 0.630 AC: 2194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	9.3
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: rs6541003; hg19: chr1-11855867;