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GeneBe

1-11790683-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PM2_SupportingBP4_ModerateBP6_ModerateBP7

The NM_005957(MTHFR):c.1968A>G(p.Pro656=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152054 control chromosomes in the gnomAD Genomes database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000040 ( 0 hom. )

Consequence

MTHFR
NM_005957 synonymous

Scores

6

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.22

Links

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
?
Very rare variant; Number of alleles below threshold, gnomad allele frequency = 0.00000658 (1/152054) while in subpopulation AFR AF= 0.0000242 (1/41394). AF 95% confidence interval is 0. There are 0 homozygotes in gnomad. There are 1 alleles in male gnomad subpopulation. Median coverage is 33. This position pass quality control queck.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.070465684).
BP6
?
Variant 1:11790683-T>C is Benign according to our data. Variant chr1-11790683-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1087028. Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-2.22 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MTHFRNM_005957.5 linkuse as main transcriptc.1968A>G p.Pro656= synonymous_variant 12/12 ENST00000376590.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MTHFRENST00000376590.9 linkuse as main transcriptc.1968A>G p.Pro656= synonymous_variant 12/121 NM_005957.5 A1P42898-1

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152054
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251238
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135792
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461800
Hom.:
0
AF XY:
0.00000825
AC XY:
6
AN XY:
727184
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.0000331
Alfa
AF:
0.0000658
Hom.:
0
Bravo
AF:
0.0000151
ExAC
AF:
0.00000824
AC:
1

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
Likely benign, criteria provided, single submitterclinical testingInvitaeMar 13, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.94
Cadd
Benign
0.52
Dann
Benign
0.59
FATHMM_MKL
Benign
0.0021
N
LIST_S2
Benign
0.22
T
MetaRNN
Benign
0.070
T
MutationTaster
Benign
1.0
N;N;N;N
GERP RS
-5.2

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: rs774321998; hg19: chr1-11850740;