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GeneBe

1-11788023-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_001010881.2(C1orf167):c.3824G>A(p.Ser1275Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00133 in 1,301,232 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0014 ( 3 hom. )

Consequence

C1orf167
NM_001010881.2 missense

Scores

1
17

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 1.51
Variant links:
Genes affected
C1orf167 (HGNC:25262): (chromosome 1 open reading frame 167) Implicated in coronary artery disease. [provided by Alliance of Genome Resources, Apr 2022]
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0053456426).
BP6
Variant 1-11788023-G-A is Benign according to our data. Variant chr1-11788023-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 292189.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
C1orf167NM_001010881.2 linkuse as main transcriptc.3824G>A p.Ser1275Asn missense_variant 18/21 ENST00000688073.1
MTHFRNM_005957.5 linkuse as main transcriptc.*2657C>T 3_prime_UTR_variant 12/12 ENST00000376590.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
C1orf167ENST00000688073.1 linkuse as main transcriptc.3824G>A p.Ser1275Asn missense_variant 18/21 NM_001010881.2 A2
MTHFRENST00000376590.9 linkuse as main transcriptc.*2657C>T 3_prime_UTR_variant 12/121 NM_005957.5 A1P42898-1

Frequencies

GnomAD3 genomes
AF:
0.00120
AC:
182
AN:
152232
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000314
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000327
Gnomad ASJ
AF:
0.00173
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.000942
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.00207
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.00125
AC:
185
AN:
147914
Hom.:
1
AF XY:
0.00119
AC XY:
95
AN XY:
79538
show subpopulations
Gnomad AFR exome
AF:
0.000447
Gnomad AMR exome
AF:
0.000294
Gnomad ASJ exome
AF:
0.00199
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000996
Gnomad FIN exome
AF:
0.00175
Gnomad NFE exome
AF:
0.00184
Gnomad OTH exome
AF:
0.00118
GnomAD4 exome
AF:
0.00135
AC:
1551
AN:
1148882
Hom.:
3
Cov.:
31
AF XY:
0.00135
AC XY:
763
AN XY:
563252
show subpopulations
Gnomad4 AFR exome
AF:
0.000206
Gnomad4 AMR exome
AF:
0.000253
Gnomad4 ASJ exome
AF:
0.00179
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00108
Gnomad4 FIN exome
AF:
0.00165
Gnomad4 NFE exome
AF:
0.00143
Gnomad4 OTH exome
AF:
0.00133
GnomAD4 genome
AF:
0.00119
AC:
182
AN:
152350
Hom.:
0
Cov.:
33
AF XY:
0.00102
AC XY:
76
AN XY:
74502
show subpopulations
Gnomad4 AFR
AF:
0.000313
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00173
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.000942
Gnomad4 NFE
AF:
0.00207
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.00155
Hom.:
0
Bravo
AF:
0.00110
TwinsUK
AF:
0.00216
AC:
8
ALSPAC
AF:
0.00104
AC:
4
ExAC
AF:
0.00118
AC:
28
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

Homocystinuria due to methylene tetrahydrofolate reductase deficiency Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingBaylor GeneticsJun 11, 2018This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenFeb 01, 2024C1orf167: BP4 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Benign
-0.61
T
BayesDel_noAF
Benign
-0.65
Cadd
Benign
8.3
Dann
Benign
0.87
DEOGEN2
Benign
0.0018
T
Eigen
Benign
-0.76
Eigen_PC
Benign
-0.83
FATHMM_MKL
Benign
0.28
N
LIST_S2
Benign
0.36
T
M_CAP
Benign
0.031
D
MetaRNN
Benign
0.0053
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.69
N
MutationTaster
Benign
1.0
N;N;N;N
PROVEAN
Benign
-0.94
N
REVEL
Benign
0.071
Sift
Pathogenic
0.0
D
Sift4G
Benign
0.14
T
Polyphen
0.57
P
Vest4
0.044
MVP
0.067
MPC
0.55
ClinPred
0.027
T
GERP RS
2.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.027
gMVP
0.078

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: rs371188005; hg19: chr1-11848080; COSMIC: COSV57172189; COSMIC: COSV57172189; API