1-11787392-GC-AT

Variant names:

• chr1-11787392-GC-AT
• NM_001010881.2:c.3572_3573delGCinsAT
• C1orf167 p.Arg1191His

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001010881.2(C1orf167):​c.3572_3573delGCinsAT​(p.Arg1191His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: C1orf167 NM_001010881.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.316
• Publications: 0 publications found

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]

MTHFR Gene-Disease associations (from GenCC):

• homocystinuria due to methylene tetrahydrofolate reductase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010881.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1orf167	NM_001010881.2	MANE Select	c.3572_3573delGCinsAT	p.Arg1191His	missense	N/A	NP_001010881.1	Q5SNV9-1
	MTHFR	NM_005957.5	MANE Select	c.*3287_*3288delGCinsAT		3_prime_UTR	Exon 12 of 12	NP_005948.3
	MTHFR	NM_001330358.2		c.*3287_*3288delGCinsAT		3_prime_UTR	Exon 12 of 12	NP_001317287.1	P42898-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1orf167	ENST00000688073.1	MANE Select	c.3572_3573delGCinsAT	p.Arg1191His	missense	N/A	ENSP00000510540.1	Q5SNV9-1
	C1orf167	ENST00000444493.5	TSL:1	c.1070_1071delGCinsAT	p.Arg357His	missense	N/A	ENSP00000398213.1	H0Y5F2
	C1orf167	ENST00000449278.1	TSL:1	c.899_900delGCinsAT	p.Arg300His	missense	N/A	ENSP00000399272.1	H0Y5L4

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.32

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-11847449;