Variant chr1-11790308-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.874

Variant links:

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]

MTHFR links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
MTHFR	NM_005957.5 linkuse as main transcript	c.*372A>C		3_prime_UTR_variant	12/12	ENST00000376590.9	NP_005948.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTHFR	ENST00000376590.9 linkuse as main transcript	c.*372A>C		3_prime_UTR_variant	12/12	1	NM_005957.5	ENSP00000365775	A1	P42898-1

Frequencies

GnomAD3 genomes

AF:

0.632

AC:

96038

AN:

151972

Hom.:

31075

Cov.:

show subpopulations

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.:

AF XY:

0.670

AC XY:

130689

AN XY:

195180

show subpopulations

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.:

AF XY:

0.632

AC XY:

47033

AN XY:

74362

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Homocystinuria due to methylene tetrahydrofolate reductase deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over