rs1537516
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
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
NM_005957.5 3_prime_UTR
Scores
2
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MTHFR | NM_005957.5 | c.*2876C>T | 3_prime_UTR_variant | 12/12 | ENST00000376590.9 | NP_005948.3 | ||
C1orf167 | NM_001010881.2 | c.3674-69G>A | intron_variant | ENST00000688073.1 | NP_001010881.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MTHFR | ENST00000376590 | c.*2876C>T | 3_prime_UTR_variant | 12/12 | 1 | NM_005957.5 | ENSP00000365775.3 | |||
C1orf167 | ENST00000688073.1 | c.3674-69G>A | intron_variant | NM_001010881.2 | ENSP00000510540.1 |
Frequencies
GnomAD3 genomes AF: 0.0971 AC: 14768AN: 152076Hom.: 786 Cov.: 33
GnomAD3 genomes
AF:
AC:
14768
AN:
152076
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.109 AC: 111954AN: 1029766Hom.: 6503 Cov.: 29 AF XY: 0.110 AC XY: 54309AN XY: 492024
GnomAD4 exome
AF:
AC:
111954
AN:
1029766
Hom.:
Cov.:
29
AF XY:
AC XY:
54309
AN XY:
492024
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0972 AC: 14792AN: 152194Hom.: 789 Cov.: 33 AF XY: 0.0986 AC XY: 7336AN XY: 74410
GnomAD4 genome
AF:
AC:
14792
AN:
152194
Hom.:
Cov.:
33
AF XY:
AC XY:
7336
AN XY:
74410
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
513
AN:
3476
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at