chr1-11788023-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

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

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]

C1orf167 links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 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}.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1orf167	NM_001010881.2 link	c.3824G>A	p.Ser1275Asn	missense_variant	Exon 18 of 21	ENST00000688073.1	NP_001010881.1	Q5SNV9A2VCK6A0A8I5KXP5Q8NDG0
MTHFR	NM_005957.5 link	c.*2657C>T		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
C1orf167	ENST00000688073.1 link	c.3824G>A	p.Ser1275Asn	missense_variant	Exon 18 of 21		NM_001010881.2	ENSP00000510540.1		A0A8I5KXP5
MTHFR	ENST00000376590 link	c.*2657C>T		3_prime_UTR_variant	Exon 12 of 12	1	NM_005957.5	ENSP00000365775.3		P42898-1

Frequencies

GnomAD3 genomes

AF:

0.00120

AC:

182

AN:

152232

Hom.:

Cov.:

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.:

AF XY:

0.00119

AC XY:

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.:

Cov.:

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.:

Cov.:

AF XY:

0.00102

AC XY:

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.:

Bravo

AF:

0.00110

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00104

AC:

ExAC

AF:

0.00118

AC:

Asia WGS

AF:

0.000577

AC:

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

Jun 11, 2018

Baylor Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -

not provided

Benign:1

Feb 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

C1orf167: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.65

CADD

Benign

8.3

DANN

Benign

0.87

DEOGEN2

Benign

0.0018

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.36

M_CAP

Benign

0.031

MetaRNN

Benign

0.0053

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PROVEAN

Benign

-0.94

REVEL

Benign

0.071

Sift

Pathogenic

0.0

Sift4G

Benign

0.14

Polyphen

0.57

Vest4

0.044

MVP

0.067

MPC

0.55

ClinPred

0.027

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over