chr1-11786035-G-GTT

Variant names:

• chr1-11786035-G-GTT
• rs55740775
• NM_005957.5:c.*4643_*4644dupAA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1

The NM_005957.5(MTHFR):​c.*4643_*4644dupAA 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 0.0012 (0 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: MTHFR NM_005957.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.535

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 Likely_benign. Variant got -4 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00119 (178/149368) while in subpopulation EAS AF= 0.00195 (10/5134). AF 95% confidence interval is 0.00128. There are 0 homozygotes in gnomad4. There are 97 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTHFR	NM_005957.5	c.*4643_*4644dupAA		3_prime_UTR_variant	Exon 12 of 12	ENST00000376590.9	NP_005948.3
C1orf167	NM_001010881.2	c.3567+756_3567+757dupTT		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.*4643_*4644dupAA		3_prime_UTR_variant	Exon 12 of 12	1	NM_005957.5	ENSP00000365775.3
C1orf167	ENST00000688073.1	c.3567+756_3567+757dupTT		intron_variant	Intron 16 of 20		NM_001010881.2	ENSP00000510540.1

Frequencies

GnomAD3 genomes AF: 0.00119 AC: 177 AN: 149284 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00157

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000865

Gnomad ASJ AF: 0.000582

Gnomad EAS AF: 0.00194

Gnomad SAS AF: 0.000211

Gnomad FIN AF: 0.00423

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000625

Gnomad OTH AF: 0.00196

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

GnomAD4 genome AF: 0.00119 AC: 178 AN: 149368 Hom.: 0 Cov.: 0 AF XY: 0.00133 AC XY: 97 AN XY: 72720

Gnomad4 AFR AF: 0.00159

Gnomad4 AMR AF: 0.000864

Gnomad4 ASJ AF: 0.000582

Gnomad4 EAS AF: 0.00195

Gnomad4 SAS AF: 0.000212

Gnomad4 FIN AF: 0.00423

Gnomad4 NFE AF: 0.000625

Gnomad4 OTH AF: 0.00195

Alfa AF: 0.000226 Hom.: 2192

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: rs55740775; hg19: chr1-11846092;