rs13306556

Positions:

• chr1-11792053-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005957.5(MTHFR):​c.1632+225G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,274 control chromosomes in the GnomAD database, including 896 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.11 (896 hom., cov: 33)
• Consequence: MTHFR NM_005957.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0900

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 1-11792053-C-T is Benign according to our data. Variant chr1-11792053-C-T is described in ClinVar as [Benign]. Clinvar id is 1253969.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTHFR	NM_005957.5	c.1632+225G>A		intron_variant		ENST00000376590.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTHFR	ENST00000376590.9	c.1632+225G>A		intron_variant		1	NM_005957.5	A1

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15973 AN: 152156 Hom.: 895 Cov.: 33

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0691

Gnomad ASJ AF: 0.0366

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0894

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

GnomAD4 genome AF: 0.105 AC: 15995 AN: 152274 Hom.: 896 Cov.: 33 AF XY: 0.106 AC XY: 7892 AN XY: 74454

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.0691

Gnomad4 ASJ AF: 0.0366

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.0894

Alfa AF: 0.0958 Hom.: 751

Bravo AF: 0.0964

Asia WGS AF: 0.146 AC: 508 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 13, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.7
DANN	Benign	0.69

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: rs13306556; hg19: chr1-11852110; COSMIC: COSV57173240; COSMIC: COSV57173240;