1-11786602-ATTTTTTTTT-ATTTTTTTTTTTT

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_005957.5(MTHFR):​c.*4075_*4077dupAAA 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 0.0064 (9 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.

• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00645 (917/142194) while in subpopulation SAS AF= 0.0183 (80/4372). AF 95% confidence interval is 0.0151. There are 9 homozygotes in gnomad4. There are 438 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTHFR	NM_005957.5	c.*4075_*4077dupAAA		3_prime_UTR_variant	Exon 12 of 12	ENST00000376590.9	NP_005948.3
C1orf167	NM_001010881.2	c.3568-769_3568-767dupTTT		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.*4075_*4077dupAAA		3_prime_UTR_variant	Exon 12 of 12	1	NM_005957.5	ENSP00000365775.3
C1orf167	ENST00000688073.1	c.3568-769_3568-767dupTTT		intron_variant	Intron 16 of 20		NM_001010881.2	ENSP00000510540.1

Frequencies

GnomAD3 genomes AF: 0.00642 AC: 913 AN: 142164 Hom.: 8 Cov.: 0

Gnomad AFR AF: 0.00174

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00991

Gnomad ASJ AF: 0.00297

Gnomad EAS AF: 0.00710

Gnomad SAS AF: 0.0184

Gnomad FIN AF: 0.00175

Gnomad MID AF: 0.0135

Gnomad NFE AF: 0.00825

Gnomad OTH AF: 0.0102

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

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.00645 AC: 917 AN: 142194 Hom.: 9 Cov.: 0 AF XY: 0.00640 AC XY: 438 AN XY: 68428

Gnomad4 AFR AF: 0.00173

Gnomad4 AMR AF: 0.00991

Gnomad4 ASJ AF: 0.00297

Gnomad4 EAS AF: 0.00712

Gnomad4 SAS AF: 0.0183

Gnomad4 FIN AF: 0.00175

Gnomad4 NFE AF: 0.00825

Gnomad4 OTH AF: 0.0132

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;