NM_005957.5:c.*2876C>G

Variant names:

• chr1-11787804-G-C
• rs1537516
• NM_005957.5:c.*2876C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005957.5(MTHFR):​c.*2876C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000097 in 1,031,238 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 9.7e-7 (0 hom.)
• Consequence: MTHFR NM_005957.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0150
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005957.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTHFR	NM_005957.5	MANE Select	c.*2876C>G		3_prime_UTR	Exon 12 of 12	NP_005948.3
	C1orf167	NM_001010881.2	MANE Select	c.3674-69G>C		intron	N/A	NP_001010881.1
	MTHFR	NM_001330358.2		c.*2876C>G		3_prime_UTR	Exon 12 of 12	NP_001317287.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTHFR	ENST00000376590.9	TSL:1 MANE Select	c.*2876C>G		3_prime_UTR	Exon 12 of 12	ENSP00000365775.3
	MTHFR	ENST00000376592.6	TSL:1	c.*2876C>G		3_prime_UTR	Exon 12 of 12	ENSP00000365777.1
	C1orf167	ENST00000688073.1	MANE Select	c.3674-69G>C		intron	N/A	ENSP00000510540.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 9.70e-7 AC: 1 AN: 1031238 Hom.: 0 Cov.: 29 AF XY: 0.00000203 AC XY: 1 AN XY: 492746

African (AFR) AF: 0.00 AC: 0 AN: 20864

American (AMR) AF: 0.00 AC: 0 AN: 10618

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9248

East Asian (EAS) AF: 0.00 AC: 0 AN: 10730

South Asian (SAS) AF: 0.00 AC: 0 AN: 56698

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2286

European-Non Finnish (NFE) AF: 0.00000116 AC: 1 AN: 861298

Other (OTH) AF: 0.00 AC: 0 AN: 36102

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.0
DANN	Benign	0.53
PhyloP100		-0.015
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

Other links and lift over

dbSNP: rs1537516; hg19: chr1-11847861;