1-11788023-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001010881.2(C1orf167):ā€‹c.3824G>Cā€‹(p.Ser1275Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000284 in 1,301,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S1275N) has been classified as Likely benign.

Frequency

Genomes: š‘“ 0.000033 ( 0 hom., cov: 33)
Exomes š‘“: 0.000028 ( 0 hom. )

Consequence

C1orf167
NM_001010881.2 missense

Scores

1
17

Clinical Significance

Not reported in ClinVar

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 -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.062096804).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
C1orf167NM_001010881.2 linkc.3824G>C p.Ser1275Thr missense_variant Exon 18 of 21 ENST00000688073.1 NP_001010881.1 Q5SNV9A2VCK6A0A8I5KXP5Q8NDG0
MTHFRNM_005957.5 linkc.*2657C>G 3_prime_UTR_variant Exon 12 of 12 ENST00000376590.9 NP_005948.3 P42898-1Q8IU67Q59GJ6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
C1orf167ENST00000688073.1 linkc.3824G>C p.Ser1275Thr missense_variant Exon 18 of 21 NM_001010881.2 ENSP00000510540.1 A0A8I5KXP5
MTHFRENST00000376590 linkc.*2657C>G 3_prime_UTR_variant Exon 12 of 12 1 NM_005957.5 ENSP00000365775.3 P42898-1

Frequencies

GnomAD3 genomes
AF:
0.0000328
AC:
5
AN:
152232
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000270
AC:
4
AN:
147914
Hom.:
0
AF XY:
0.0000377
AC XY:
3
AN XY:
79538
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:
0.0000716
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000279
AC:
32
AN:
1148882
Hom.:
0
Cov.:
31
AF XY:
0.0000302
AC XY:
17
AN XY:
563252
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000326
Gnomad4 OTH exome
AF:
0.0000482
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152232
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74374
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
6.8
DANN
Benign
0.84
DEOGEN2
Benign
0.0016
T
Eigen
Benign
-0.76
Eigen_PC
Benign
-0.82
FATHMM_MKL
Benign
0.41
N
LIST_S2
Benign
0.30
T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.062
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.34
N
PROVEAN
Benign
-0.56
N
REVEL
Benign
0.065
Sift
Pathogenic
0.0
D
Sift4G
Benign
0.89
T
Polyphen
0.57
P
Vest4
0.052
MutPred
0.17
Gain of phosphorylation at S1299 (P = 0.1082);
MVP
0.067
MPC
0.48
ClinPred
0.085
T
GERP RS
2.8
Varity_R
0.033
gMVP
0.072

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; API