GeneBe

rs777661576

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_005957.5(MTHFR):​c.1753-18G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

MTHFR
NM_005957.5 intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.339

Publications

0 publications found
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]
MTHFR Gene-Disease associations (from GenCC):
  • homocystinuria due to methylene tetrahydrofolate reductase deficiency
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.94).
BP6
Variant 1-11790916-C-A is Benign according to our data. Variant chr1-11790916-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2742066.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MTHFRNM_005957.5 linkc.1753-18G>T intron_variant Intron 11 of 11 ENST00000376590.9 NP_005948.3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MTHFRENST00000376590.9 linkc.1753-18G>T intron_variant Intron 11 of 11 1 NM_005957.5 ENSP00000365775.3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
1450738
Hom.:
0
Cov.:
28
AF XY:
0.00
AC XY:
0
AN XY:
722240
African (AFR)
AF:
0.00
AC:
0
AN:
33208
American (AMR)
AF:
0.00
AC:
0
AN:
44714
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26084
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39618
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85972
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53344
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5728
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1102094
Other (OTH)
AF:
0.00
AC:
0
AN:
59976
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

Homocystinuria due to methylene tetrahydrofolate reductase deficiency Benign:1
Apr 09, 2023
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.94
CADD
Benign
1.5
DANN
Benign
0.75
PhyloP100
-0.34
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

Other links and lift over

dbSNP: rs777661576; hg19: chr1-11850973; API