rs1537516

chr1-11787804-G-A

Variant summary

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

The NM_005957.5(MTHFR):c.*2876C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,181,960 control chromosomes in the GnomAD database, including 7,292 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 0.097 (789 hom., cov: 33)
  • Exomes 𝑓: 0.11 (6503 hom.)
• Consequence: MTHFR NM_005957.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0150

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]

C1orf167 (HGNC:25262): (chromosome 1 open reading frame 167) Implicated in coronary artery disease. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTHFR	NM_005957.5	c.*2876C>T		3_prime_UTR_variant	12/12	ENST00000376590.9
C1orf167	NM_001010881.2	c.3674-69G>A		intron_variant		ENST00000688073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTHFR	ENST00000376590.9	c.*2876C>T		3_prime_UTR_variant	12/12	1	NM_005957.5	A1
C1orf167	ENST00000688073.1	c.3674-69G>A		intron_variant			NM_001010881.2	A2

Frequencies

GnomAD3 genomes AF: 0.0971 AC: 14768 AN: 152076 Hom.: 786 Cov.: 33

Gnomad AFR AF: 0.0818

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0665

Gnomad ASJ AF: 0.0326

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.0806

GnomAD4 exome AF: 0.109 AC: 111954 AN: 1029766 Hom.: 6503 Cov.: 29 AF XY: 0.110 AC XY: 54309 AN XY: 492024

Gnomad4 AFR exome AF: 0.0733

Gnomad4 AMR exome AF: 0.0672

Gnomad4 ASJ exome AF: 0.0345

Gnomad4 EAS exome AF: 0.122

Gnomad4 SAS exome AF: 0.175

Gnomad4 FIN exome AF: 0.118

Gnomad4 NFE exome AF: 0.106

Gnomad4 OTH exome AF: 0.109

GnomAD4 genome AF: 0.0972 AC: 14792 AN: 152194 Hom.: 789 Cov.: 33 AF XY: 0.0986 AC XY: 7336 AN XY: 74410

Gnomad4 AFR AF: 0.0821

Gnomad4 AMR AF: 0.0665

Gnomad4 ASJ AF: 0.0326

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.0807

Alfa AF: 0.0971 Hom.: 469

Bravo AF: 0.0879

Asia WGS AF: 0.148 AC: 513 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	3.4
Dann	Benign	0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1537516; hg19: chr1-11847861;