1-11786602-A-ATT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_005957.5(MTHFR):​c.*4077_*4078insAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.12 ( 1242 hom., cov: 0)
Exomes 𝑓: 0.25 ( 0 hom. )

Consequence

MTHFR
NM_005957.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.308
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]
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 -8 ACMG points.

BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MTHFRNM_005957.5 linkuse as main transcriptc.*4077_*4078insAA 3_prime_UTR_variant 12/12 ENST00000376590.9
C1orf167NM_001010881.2 linkuse as main transcriptc.3568-768_3568-767dup intron_variant ENST00000688073.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MTHFRENST00000376590.9 linkuse as main transcriptc.*4077_*4078insAA 3_prime_UTR_variant 12/121 NM_005957.5 A1P42898-1
C1orf167ENST00000688073.1 linkuse as main transcriptc.3568-768_3568-767dup intron_variant NM_001010881.2 A2

Frequencies

GnomAD3 genomes
AF:
0.115
AC:
16356
AN:
141838
Hom.:
1244
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.0278
Gnomad AMI
AF:
0.192
Gnomad AMR
AF:
0.0875
Gnomad ASJ
AF:
0.216
Gnomad EAS
AF:
0.0867
Gnomad SAS
AF:
0.175
Gnomad FIN
AF:
0.131
Gnomad MID
AF:
0.205
Gnomad NFE
AF:
0.162
Gnomad OTH
AF:
0.128
GnomAD4 exome
AF:
0.250
AC:
1
AN:
4
Hom.:
0
Cov.:
0
AC XY:
0
AN XY:
0
show subpopulations
Gnomad4 NFE exome
AF:
0.250
GnomAD4 genome
AF:
0.115
AC:
16341
AN:
141868
Hom.:
1242
Cov.:
0
AF XY:
0.112
AC XY:
7674
AN XY:
68236
show subpopulations
Gnomad4 AFR
AF:
0.0277
Gnomad4 AMR
AF:
0.0874
Gnomad4 ASJ
AF:
0.216
Gnomad4 EAS
AF:
0.0870
Gnomad4 SAS
AF:
0.176
Gnomad4 FIN
AF:
0.131
Gnomad4 NFE
AF:
0.162
Gnomad4 OTH
AF:
0.127

ClinVar

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

Submissions by phenotype

Neural tube defects, folate-sensitive Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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: rs55780505; hg19: chr1-11846659; API