rs17421511

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_005957.5(MTHFR):​c.587-1332C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,206 control chromosomes in the GnomAD database, including 1,487 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.13 ( 1487 hom., cov: 32)

Consequence

MTHFR
NM_005957.5 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.216
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant 1-11797731-G-A is Benign according to our data. Variant chr1-11797731-G-A is described in ClinVar as [Benign]. Clinvar id is 1168301.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MTHFRNM_005957.5 linkuse as main transcriptc.587-1332C>T intron_variant ENST00000376590.9 NP_005948.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MTHFRENST00000376590.9 linkuse as main transcriptc.587-1332C>T intron_variant 1 NM_005957.5 ENSP00000365775 A1P42898-1

Frequencies

GnomAD3 genomes
AF:
0.127
AC:
19367
AN:
152088
Hom.:
1489
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0439
Gnomad AMI
AF:
0.200
Gnomad AMR
AF:
0.103
Gnomad ASJ
AF:
0.209
Gnomad EAS
AF:
0.0980
Gnomad SAS
AF:
0.206
Gnomad FIN
AF:
0.169
Gnomad MID
AF:
0.253
Gnomad NFE
AF:
0.167
Gnomad OTH
AF:
0.148
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.127
AC:
19365
AN:
152206
Hom.:
1487
Cov.:
32
AF XY:
0.128
AC XY:
9515
AN XY:
74410
show subpopulations
Gnomad4 AFR
AF:
0.0439
Gnomad4 AMR
AF:
0.103
Gnomad4 ASJ
AF:
0.209
Gnomad4 EAS
AF:
0.0980
Gnomad4 SAS
AF:
0.207
Gnomad4 FIN
AF:
0.169
Gnomad4 NFE
AF:
0.167
Gnomad4 OTH
AF:
0.148
Alfa
AF:
0.141
Hom.:
307
Bravo
AF:
0.118
Asia WGS
AF:
0.152
AC:
530
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Homocystinuria due to methylene tetrahydrofolate reductase deficiency Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 01, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
4.3
DANN
Benign
0.60

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs17421511; hg19: chr1-11857788; COSMIC: COSV64877190; COSMIC: COSV64877190; API