1-11786602-ATTTTTTTTT-ATTT

Variant names:

• chr1-11786602-ATTTTTT-A
• rs55780505
• NM_005957.5:c.*4072_*4077delAAAAAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_005957.5(MTHFR):​c.*4072_*4077delAAAAAA 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 0.030 (190 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MTHFR NM_005957.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308

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 Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0978 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTHFR	NM_005957.5	c.*4072_*4077delAAAAAA		3_prime_UTR_variant	Exon 12 of 12	ENST00000376590.9	NP_005948.3
C1orf167	NM_001010881.2	c.3568-772_3568-767delTTTTTT		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.*4072_*4077delAAAAAA		3_prime_UTR_variant	Exon 12 of 12	1	NM_005957.5	ENSP00000365775.3
C1orf167	ENST00000688073.1	c.3568-772_3568-767delTTTTTT		intron_variant	Intron 16 of 20		NM_001010881.2	ENSP00000510540.1

Frequencies

GnomAD3 genomes AF: 0.0296 AC: 4203 AN: 142154 Hom.: 190 Cov.: 0

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0109

Gnomad ASJ AF: 0.0157

Gnomad EAS AF: 0.00125

Gnomad SAS AF: 0.00136

Gnomad FIN AF: 0.000250

Gnomad MID AF: 0.00676

Gnomad NFE AF: 0.000885

Gnomad OTH AF: 0.0236

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

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0296 AC: 4208 AN: 142182 Hom.: 190 Cov.: 0 AF XY: 0.0295 AC XY: 2019 AN XY: 68428

Gnomad4 AFR AF: 0.100

Gnomad4 AMR AF: 0.0109

Gnomad4 ASJ AF: 0.0157

Gnomad4 EAS AF: 0.00126

Gnomad4 SAS AF: 0.00114

Gnomad4 FIN AF: 0.000250

Gnomad4 NFE AF: 0.000885

Gnomad4 OTH AF: 0.0234

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs55780505; hg19: chr1-11846659;