1-11786602-ATTT-A

Variant names:

• chr1-11786602-ATTT-A
• rs55780505
• NM_005957.5:c.*4075_*4077delAAA

Variant summary

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

The NM_001330358.2(MTHFR):​c.*4075_*4077delAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.016 (37 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MTHFR NM_001330358.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308
• Publications: 3 publications found

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

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330358.2. 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
	MTHFR	NM_005957.5	MANE Select	c.*4075_*4077delAAA		3_prime_UTR	Exon 12 of 12	NP_005948.3
	C1orf167	NM_001010881.2	MANE Select	c.3568-769_3568-767delTTT		intron	N/A	NP_001010881.1
	MTHFR	NM_001330358.2		c.*4075_*4077delAAA		3_prime_UTR	Exon 12 of 12	NP_001317287.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTHFR	ENST00000376590.9	TSL:1 MANE Select	c.*4075_*4077delAAA		3_prime_UTR	Exon 12 of 12	ENSP00000365775.3
	MTHFR	ENST00000376592.6	TSL:1	c.*4075_*4077delAAA		3_prime_UTR	Exon 12 of 12	ENSP00000365777.1
	C1orf167	ENST00000688073.1	MANE Select	c.3568-769_3568-767delTTT		intron	N/A	ENSP00000510540.1

Frequencies

GnomAD3 genomes AF: 0.0158 AC: 2238 AN: 142082 Hom.: 37 Cov.: 0

Gnomad AFR AF: 0.00933

Gnomad AMI AF: 0.00226

Gnomad AMR AF: 0.00887

Gnomad ASJ AF: 0.00356

Gnomad EAS AF: 0.0111

Gnomad SAS AF: 0.0243

Gnomad FIN AF: 0.0316

Gnomad MID AF: 0.0101

Gnomad NFE AF: 0.0199

Gnomad OTH AF: 0.0108

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 4 Hom.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0158 AC: 2240 AN: 142110 Hom.: 37 Cov.: 0 AF XY: 0.0160 AC XY: 1095 AN XY: 68388

African (AFR) AF: 0.00937 AC: 362 AN: 38644

American (AMR) AF: 0.00886 AC: 127 AN: 14326

Ashkenazi Jewish (ASJ) AF: 0.00356 AC: 12 AN: 3370

East Asian (EAS) AF: 0.0111 AC: 53 AN: 4770

South Asian (SAS) AF: 0.0242 AC: 106 AN: 4376

European-Finnish (FIN) AF: 0.0316 AC: 252 AN: 7984

Middle Eastern (MID) AF: 0.0109 AC: 3 AN: 274

European-Non Finnish (NFE) AF: 0.0199 AC: 1302 AN: 65514

Other (OTH) AF: 0.0107 AC: 21 AN: 1966

Alfa AF: 0.0272 Hom.: 551

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.31
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs55780505; hg19: chr1-11846659;