1-11786602-AT-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_001330358.2(MTHFR):​c.*4077delA 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 0.0027 (0 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: Likely_benign. The variant received -4 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00272 (387/142214) while in subpopulation AFR AF = 0.00906 (350/38648). AF 95% confidence interval is 0.00827. There are 0 homozygotes in GnomAd4. There are 186 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

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.*4077delA		3_prime_UTR	Exon 12 of 12	NP_005948.3
	C1orf167	NM_001010881.2	MANE Select	c.3568-767delT		intron	N/A	NP_001010881.1
	MTHFR	NM_001330358.2		c.*4077delA		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.*4077delA		3_prime_UTR	Exon 12 of 12	ENSP00000365775.3
	MTHFR	ENST00000376592.6	TSL:1	c.*4077delA		3_prime_UTR	Exon 12 of 12	ENSP00000365777.1
	C1orf167	ENST00000688073.1	MANE Select	c.3568-767delT		intron	N/A	ENSP00000510540.1

Frequencies

GnomAD3 genomes AF: 0.00271 AC: 385 AN: 142184 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00902

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00119

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000209

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000623

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000122

Gnomad OTH AF: 0.00307

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

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 AF: 0.00272 AC: 387 AN: 142214 Hom.: 0 Cov.: 0 AF XY: 0.00272 AC XY: 186 AN XY: 68444

African (AFR) AF: 0.00906 AC: 350 AN: 38648

American (AMR) AF: 0.00119 AC: 17 AN: 14338

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3370

East Asian (EAS) AF: 0.000210 AC: 1 AN: 4772

South Asian (SAS) AF: 0.00 AC: 0 AN: 4376

European-Finnish (FIN) AF: 0.000623 AC: 5 AN: 8022

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 274

European-Non Finnish (NFE) AF: 0.000122 AC: 8 AN: 65560

Other (OTH) AF: 0.00305 AC: 6 AN: 1968

Alfa AF: 0.00 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;