1-11788203-CCTT-C

Variant names:

• chr1-11788203-CCTT-C
• rs886045180
• NM_001010881.2:c.3906_3908delTCT

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PM4_Supporting

The NM_001010881.2(C1orf167):​c.3906_3908delTCT​(p.Leu1303del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000348 in 1,148,240 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: C1orf167 NM_001010881.2 disruptive_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.716

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001010881.2. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1orf167	NM_001010881.2	c.3906_3908delTCT	p.Leu1303del	disruptive_inframe_deletion	Exon 19 of 21	ENST00000688073.1	NP_001010881.1
MTHFR	NM_005957.5	c.*2474_*2476delAAG		3_prime_UTR_variant	Exon 12 of 12	ENST00000376590.9	NP_005948.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1orf167	ENST00000688073.1	c.3906_3908delTCT	p.Leu1303del	disruptive_inframe_deletion	Exon 19 of 21		NM_001010881.2	ENSP00000510540.1
MTHFR	ENST00000376590	c.*2474_*2476delAAG		3_prime_UTR_variant	Exon 12 of 12	1	NM_005957.5	ENSP00000365775.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000348 AC: 4 AN: 1148240 Hom.: 0 AF XY: 0.00000534 AC XY: 3 AN XY: 562028

Gnomad4 AFR exome AF: 0.00 AC: 0 AN: 24344

Gnomad4 AMR exome AF: 0.00 AC: 0 AN: 28190

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 15918

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 12712

Gnomad4 SAS exome AF: 0.00 AC: 0 AN: 76098

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 27330

Gnomad4 NFE exome AF: 0.00000436 AC: 4 AN: 917926

Gnomad4 Remaining exome AF: 0.00 AC: 0 AN: 41342

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Neural tube defects, folate-sensitive Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs886045180; hg19: chr1-11848260;