1-11786618-TTTTG-T

Variant names:

• chr1-11786618-TTTTG-T
• rs886045172
• NM_005957.5:c.*4058_*4061delCAAA

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_005957.5(MTHFR):​c.*4058_*4061delCAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000090 (0 hom., cov: 25)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MTHFR NM_005957.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.748

Genes affected

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]

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTHFR	NM_005957.5	c.*4058_*4061delCAAA		3_prime_UTR_variant	Exon 12 of 12	ENST00000376590.9	NP_005948.3
C1orf167	NM_001010881.2	c.3568-768_3568-765delTTGT		intron_variant	Intron 16 of 20	ENST00000688073.1	NP_001010881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTHFR	ENST00000376590	c.*4058_*4061delCAAA		3_prime_UTR_variant	Exon 12 of 12	1	NM_005957.5	ENSP00000365775.3
C1orf167	ENST00000688073.1	c.3568-768_3568-765delTTGT		intron_variant	Intron 16 of 20		NM_001010881.2	ENSP00000510540.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 10 AN: 111598 Hom.: 0 Cov.: 25 FAILED QC

Gnomad AFR AF: 0.0000956

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000146

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000780

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 24 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 16

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000896 AC: 10 AN: 111598 Hom.: 0 Cov.: 25 AF XY: 0.0000932 AC XY: 5 AN XY: 53676

Gnomad4 AFR AF: 0.0000956

Gnomad4 AMR AF: 0.000197

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000146

Gnomad4 NFE AF: 0.0000780

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000307 Hom.: 0

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

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: rs886045172; hg19: chr1-11846675;