rs6541003

Variant names:

• chr1-11795810-G-A
• rs6541003
• NM_005957.5:c.780+396C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-11795810-G-A
• chr1-11795810-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 27 publications found

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]

MTHFR Gene-Disease associations (from GenCC):

• homocystinuria due to methylene tetrahydrofolate reductase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MTHFR	NM_005957.5	c.780+396C>T		intron_variant	Intron 5 of 11	ENST00000376590.9	NP_005948.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTHFR	ENST00000376590.9	c.780+396C>T		intron_variant	Intron 5 of 11	1	NM_005957.5	ENSP00000365775.3

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

African (AFR) AF: 0.440 AC: 18240 AN: 41428

American (AMR) AF: 0.689 AC: 10522 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 2202 AN: 3472

East Asian (EAS) AF: 0.779 AC: 4025 AN: 5170

South Asian (SAS) AF: 0.493 AC: 2371 AN: 4814

European-Finnish (FIN) AF: 0.639 AC: 6747 AN: 10552

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.594 AC: 40387 AN: 67974

Other (OTH) AF: 0.567 AC: 1195 AN: 2108

Alfa AF: 0.592 Hom.: 50393

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
PhyloP100		0.69
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6541003; hg19: chr1-11855867;