rs1537516

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-11787804-G-A
• chr1-11787804-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 39 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
MTHFR	NM_005957.5	c.*2876C>T		3_prime_UTR_variant	Exon 12 of 12	ENST00000376590.9	NP_005948.3
C1orf167	NM_001010881.2	c.3674-69G>A		intron_variant	Intron 17 of 20	ENST00000688073.1	NP_001010881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTHFR	ENST00000376590.9	c.*2876C>T		3_prime_UTR_variant	Exon 12 of 12	1	NM_005957.5	ENSP00000365775.3
C1orf167	ENST00000688073.1	c.3674-69G>A		intron_variant	Intron 17 of 20		NM_001010881.2	ENSP00000510540.1

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

African (AFR) AF: 0.0733 AC: 1527 AN: 20844

American (AMR) AF: 0.0672 AC: 713 AN: 10618

Ashkenazi Jewish (ASJ) AF: 0.0345 AC: 319 AN: 9248

East Asian (EAS) AF: 0.122 AC: 1304 AN: 10724

South Asian (SAS) AF: 0.175 AC: 9917 AN: 56614

European-Finnish (FIN) AF: 0.118 AC: 2759 AN: 23384

Middle Eastern (MID) AF: 0.0500 AC: 114 AN: 2280

European-Non Finnish (NFE) AF: 0.106 AC: 91377 AN: 859984

Other (OTH) AF: 0.109 AC: 3924 AN: 36070

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

African (AFR) AF: 0.0821 AC: 3409 AN: 41532

American (AMR) AF: 0.0665 AC: 1016 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0326 AC: 113 AN: 3470

East Asian (EAS) AF: 0.120 AC: 622 AN: 5168

South Asian (SAS) AF: 0.195 AC: 940 AN: 4824

European-Finnish (FIN) AF: 0.129 AC: 1363 AN: 10594

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7096 AN: 68006

Other (OTH) AF: 0.0807 AC: 170 AN: 2106

Alfa AF: 0.0946 Hom.: 626

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
PhyloP100		-0.015
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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;