rs7533315

chr1-11800626-T-C

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.476-304A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.747 in 454,420 control chromosomes in the GnomAD database, including 127,735 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.75 (42583 hom., cov: 30)
  • Exomes 𝑓: 0.75 (85152 hom.)
• Consequence: MTHFR NM_005957.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.348

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=-0.86).
• BP6: Variant 1-11800626-T-C is Benign according to our data. Variant chr1-11800626-T-C is described in ClinVar as [Benign]. Clinvar id is 1249614.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTHFR	NM_005957.5	c.476-304A>G		intron_variant		ENST00000376590.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTHFR	ENST00000376590.9	c.476-304A>G		intron_variant		1	NM_005957.5	A1

Frequencies

GnomAD3 genomes AF: 0.747 AC: 113368 AN: 151808 Hom.: 42553 Cov.: 30

Gnomad AFR AF: 0.692

Gnomad AMI AF: 0.699

Gnomad AMR AF: 0.815

Gnomad ASJ AF: 0.742

Gnomad EAS AF: 0.895

Gnomad SAS AF: 0.695

Gnomad FIN AF: 0.791

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.726

GnomAD4 exome AF: 0.747 AC: 226056 AN: 302494 Hom.: 85152 Cov.: 0 AF XY: 0.739 AC XY: 119629 AN XY: 161944

Gnomad4 AFR exome AF: 0.690

Gnomad4 AMR exome AF: 0.841

Gnomad4 ASJ exome AF: 0.737

Gnomad4 EAS exome AF: 0.898

Gnomad4 SAS exome AF: 0.657

Gnomad4 FIN exome AF: 0.792

Gnomad4 NFE exome AF: 0.748

Gnomad4 OTH exome AF: 0.746

GnomAD4 genome AF: 0.747 AC: 113456 AN: 151926 Hom.: 42583 Cov.: 30 AF XY: 0.749 AC XY: 55601 AN XY: 74270

Gnomad4 AFR AF: 0.692

Gnomad4 AMR AF: 0.815

Gnomad4 ASJ AF: 0.742

Gnomad4 EAS AF: 0.895

Gnomad4 SAS AF: 0.694

Gnomad4 FIN AF: 0.791

Gnomad4 NFE AF: 0.752

Gnomad4 OTH AF: 0.728

Alfa AF: 0.760 Hom.: 13492

Bravo AF: 0.747

Asia WGS AF: 0.789 AC: 2745 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

Jun 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.38
Dann	Benign	0.34

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: rs7533315; hg19: chr1-11860683;