rs17367629

Positions:

• chr1-11805179-C-T

Variant summary

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

The ENST00000413656.5(MTHFR):​c.-194G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0983 in 152,308 control chromosomes in the GnomAD database, including 790 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 0.098 (789 hom., cov: 33)
  • Exomes 𝑓: 0.17 (1 hom.)
• Consequence: MTHFR ENST00000413656.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• 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	Protein	UniProt
MTHFR	NM_005957.5	c.-14+709G>A		intron_variant		ENST00000376590.9	NP_005948.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTHFR	ENST00000376590.9	c.-14+709G>A		intron_variant		1	NM_005957.5	ENSP00000365775.3

Frequencies

GnomAD3 genomes AF: 0.0984 AC: 14976 AN: 152166 Hom.: 792 Cov.: 33

Gnomad AFR AF: 0.0945

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0678

Gnomad ASJ AF: 0.0317

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0827

GnomAD4 exome AF: 0.167 AC: 4 AN: 24 Hom.: 1 Cov.: 0 AF XY: 0.125 AC XY: 2 AN XY: 16

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.0983 AC: 14973 AN: 152284 Hom.: 789 Cov.: 33 AF XY: 0.0992 AC XY: 7389 AN XY: 74466

Gnomad4 AFR AF: 0.0943

Gnomad4 AMR AF: 0.0674

Gnomad4 ASJ AF: 0.0317

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.0828

Alfa AF: 0.0969 Hom.: 104

Bravo AF: 0.0921

Asia WGS AF: 0.128 AC: 445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.92
DANN	Benign	0.72

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17367629; hg19: chr1-11865236;