1-11786602-ATTTTTTTTT-ATTTTT

Variant names:

• chr1-11786602-ATTTT-A
• rs55780505
• NM_005957.5:c.*4074_*4077delAAAA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001330358.2(MTHFR):​c.*4074_*4077delAAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 142,024 control chromosomes in the GnomAD database, including 21,334 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.54 (21334 hom., cov: 0)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: MTHFR NM_001330358.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 1-11786602-ATTTT-A is Benign according to our data. Variant chr1-11786602-ATTTT-A is described in ClinVar as Likely_benign. ClinVar VariationId is 292164.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

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.*4074_*4077delAAAA		3_prime_UTR	Exon 12 of 12	NP_005948.3
	C1orf167	NM_001010881.2	MANE Select	c.3568-770_3568-767delTTTT		intron	N/A	NP_001010881.1
	MTHFR	NM_001330358.2		c.*4074_*4077delAAAA		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.*4074_*4077delAAAA		3_prime_UTR	Exon 12 of 12	ENSP00000365775.3
	MTHFR	ENST00000376592.6	TSL:1	c.*4074_*4077delAAAA		3_prime_UTR	Exon 12 of 12	ENSP00000365777.1
	C1orf167	ENST00000688073.1	MANE Select	c.3568-770_3568-767delTTTT		intron	N/A	ENSP00000510540.1

Frequencies

GnomAD3 genomes AF: 0.542 AC: 76895 AN: 141988 Hom.: 21344 Cov.: 0

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.594

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.759

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.524

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.556

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 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: 0.250 AC: 1 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.541 AC: 76883 AN: 142020 Hom.: 21334 Cov.: 0 AF XY: 0.546 AC XY: 37285 AN XY: 68342

African (AFR) AF: 0.386 AC: 14891 AN: 38558

American (AMR) AF: 0.690 AC: 9884 AN: 14330

Ashkenazi Jewish (ASJ) AF: 0.626 AC: 2109 AN: 3368

East Asian (EAS) AF: 0.758 AC: 3618 AN: 4772

South Asian (SAS) AF: 0.453 AC: 1979 AN: 4368

European-Finnish (FIN) AF: 0.621 AC: 4981 AN: 8024

Middle Eastern (MID) AF: 0.522 AC: 141 AN: 270

European-Non Finnish (NFE) AF: 0.575 AC: 37665 AN: 65480

Other (OTH) AF: 0.554 AC: 1090 AN: 1966

Alfa AF: 0.436 Hom.: 551

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Neural tube defects, folate-sensitive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV105170970; COSMIC: COSV105170970;