1-11790308-T-G

Position:

• chr1-11790308-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005957.5(MTHFR):​c.*372A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 530,354 control chromosomes in the GnomAD database, including 118,144 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.63 (31086 hom., cov: 33)
  • Exomes 𝑓: 0.67 (87058 hom.)
• Consequence: MTHFR NM_005957.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.874

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 1-11790308-T-G is Benign according to our data. Variant chr1-11790308-T-G is described in ClinVar as [Benign]. Clinvar id is 292223.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTHFR	NM_005957.5	c.*372A>C		3_prime_UTR_variant	12/12	ENST00000376590.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTHFR	ENST00000376590.9	c.*372A>C		3_prime_UTR_variant	12/12	1	NM_005957.5	A1

Frequencies

GnomAD3 genomes AF: 0.632 AC: 96038 AN: 151972 Hom.: 31075 Cov.: 33

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.712

Gnomad AMR AF: 0.751

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.655

GnomAD4 exome AF: 0.674 AC: 254913 AN: 378264 Hom.: 87058 Cov.: 3 AF XY: 0.670 AC XY: 130689 AN XY: 195180

Gnomad4 AFR exome AF: 0.503

Gnomad4 AMR exome AF: 0.775

Gnomad4 ASJ exome AF: 0.693

Gnomad4 EAS exome AF: 0.798

Gnomad4 SAS exome AF: 0.539

Gnomad4 FIN exome AF: 0.686

Gnomad4 NFE exome AF: 0.675

Gnomad4 OTH exome AF: 0.662

GnomAD4 genome AF: 0.632 AC: 96088 AN: 152090 Hom.: 31086 Cov.: 33 AF XY: 0.632 AC XY: 47033 AN XY: 74362

Gnomad4 AFR AF: 0.494

Gnomad4 AMR AF: 0.751

Gnomad4 ASJ AF: 0.685

Gnomad4 EAS AF: 0.775

Gnomad4 SAS AF: 0.544

Gnomad4 FIN AF: 0.671

Gnomad4 NFE AF: 0.674

Gnomad4 OTH AF: 0.653

Alfa AF: 0.647 Hom.: 9783

Bravo AF: 0.636

Asia WGS AF: 0.641 AC: 2229 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Homocystinuria due to methylene tetrahydrofolate reductase deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.24
DANN	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs4846049; hg19: chr1-11850365;