1-11786602-ATTTT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005957.5(MTHFR):c.*4074_*4077del 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_005957.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTHFR	NM_005957.5	c.*4074_*4077del		3_prime_UTR_variant	12/12	ENST00000376590.9
C1orf167	NM_001010881.2	c.3568-770_3568-767del		intron_variant		ENST00000688073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTHFR	ENST00000376590.9	c.*4074_*4077del		3_prime_UTR_variant	12/12	1	NM_005957.5	A1
C1orf167	ENST00000688073.1	c.3568-770_3568-767del		intron_variant			NM_001010881.2	A2

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

Gnomad4 NFE exome AF: 0.250

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

Gnomad4 AFR AF: 0.386

Gnomad4 AMR AF: 0.690

Gnomad4 ASJ AF: 0.626

Gnomad4 EAS AF: 0.758

Gnomad4 SAS AF: 0.453

Gnomad4 FIN AF: 0.621

Gnomad4 NFE AF: 0.575

Gnomad4 OTH AF: 0.554

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK:

Submissions by phenotype

Neural tube defects, folate-sensitive Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

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Calibrated prediction

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Splicing

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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

Publications

LitVar

Other links and lift over

dbSNP: rs55780505; hg19: chr1-11846659;