rs13306553

chr1-11800060-A-G

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.586+152T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 751,876 control chromosomes in the GnomAD database, including 4,232 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.099 (806 hom., cov: 30)
  • Exomes 𝑓: 0.10 (3426 hom.)
• Consequence: MTHFR NM_005957.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.183

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=-0.83).
• BP6: Variant 1-11800060-A-G is Benign according to our data. Variant chr1-11800060-A-G is described in ClinVar as [Benign]. Clinvar id is 1295236.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTHFR	NM_005957.5	c.586+152T>C		intron_variant		ENST00000376590.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTHFR	ENST00000376590.9	c.586+152T>C		intron_variant		1	NM_005957.5	A1

Frequencies

GnomAD3 genomes AF: 0.0994 AC: 15112 AN: 151982 Hom.: 809 Cov.: 30

Gnomad AFR AF: 0.0946

Gnomad AMI AF: 0.0484

Gnomad AMR AF: 0.0689

Gnomad ASJ AF: 0.0323

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.0827

GnomAD4 exome AF: 0.102 AC: 61121 AN: 599776 Hom.: 3426 Cov.: 6 AF XY: 0.104 AC XY: 33899 AN XY: 326380

Gnomad4 AFR exome AF: 0.0944

Gnomad4 AMR exome AF: 0.0644

Gnomad4 ASJ exome AF: 0.0353

Gnomad4 EAS exome AF: 0.103

Gnomad4 SAS exome AF: 0.143

Gnomad4 FIN exome AF: 0.112

Gnomad4 NFE exome AF: 0.102

Gnomad4 OTH exome AF: 0.103

GnomAD4 genome AF: 0.0993 AC: 15109 AN: 152100 Hom.: 806 Cov.: 30 AF XY: 0.100 AC XY: 7460 AN XY: 74366

Gnomad4 AFR AF: 0.0944

Gnomad4 AMR AF: 0.0685

Gnomad4 ASJ AF: 0.0323

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.0828

Alfa AF: 0.0997 Hom.: 134

Bravo AF: 0.0928

Asia WGS AF: 0.127 AC: 441 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

Jul 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.82
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: rs13306553; hg19: chr1-11860117;