1-11786602-ATTTTTTTTT-ATTTTTTTTTT

Variant names:

• chr1-11786602-A-AT
• rs55780505
• NM_005957.5:c.*4077dupA

Variant summary

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

The NM_005957.5(MTHFR):​c.*4077dupA 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 0.0036 (5 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 afr. gnomad4 allele frequency = 0.00363 (516/142196) while in subpopulation AFR AF= 0.00908 (351/38648). AF 95% confidence interval is 0.0083. There are 5 homozygotes in gnomad4. There are 241 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00363 AC: 516 AN: 142166 Hom.: 5 Cov.: 0

Gnomad AFR AF: 0.00910

Gnomad AMI AF: 0.0226

Gnomad AMR AF: 0.00209

Gnomad ASJ AF: 0.000297

Gnomad EAS AF: 0.00125

Gnomad SAS AF: 0.00227

Gnomad FIN AF: 0.00175

Gnomad MID AF: 0.0101

Gnomad NFE AF: 0.00111

Gnomad OTH AF: 0.00410

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: 0.00363 AC: 516 AN: 142196 Hom.: 5 Cov.: 0 AF XY: 0.00352 AC XY: 241 AN XY: 68434

Gnomad4 AFR AF: 0.00908

Gnomad4 AMR AF: 0.00209

Gnomad4 ASJ AF: 0.000297

Gnomad4 EAS AF: 0.00126

Gnomad4 SAS AF: 0.00229

Gnomad4 FIN AF: 0.00175

Gnomad4 NFE AF: 0.00111

Gnomad4 OTH AF: 0.00407

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs55780505; hg19: chr1-11846659;