Variant 1-11792243-C-T 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.1632+35G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 1,525,618 control chromosomes in the GnomAD database, including 56,824 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4505 hom., cov: 33)

Exomes 𝑓: 0.27 ( 52319 hom. )

Consequence

MTHFR
NM_005957.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.12

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:

MTHFR (HGNC:):

MTHFR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 1-11792243-C-T is Benign according to our data. Variant chr1-11792243-C-T is described in ClinVar as [Benign]. Clinvar id is 1170841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.398 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.1632+35G>A		intron_variant		ENST00000376590.9	NP_005948.3	P42898-1Q8IU67Q59GJ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTHFR	ENST00000376590.9 linkuse as main transcript	c.1632+35G>A		intron_variant		1	NM_005957.5	ENSP00000365775.3		P42898-1

Frequencies

GnomAD3 genomes

AF:

0.234

AC:

35644

AN:

152054

Hom.:

4505

Cov.:

show subpopulations

Gnomad AFR

AF:

0.161

Gnomad AMI

AF:

0.248

Gnomad AMR

AF:

0.173

Gnomad ASJ

AF:

0.246

Gnomad EAS

AF:

0.231

Gnomad SAS

AF:

0.412

Gnomad FIN

AF:

0.298

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.270

Gnomad OTH

AF:

0.236

GnomAD3 exomes

AF:

0.261

AC:

65718

AN:

251452

Hom.:

9554

AF XY:

0.274

AC XY:

37196

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.151

Gnomad AMR exome

AF:

0.139

Gnomad ASJ exome

AF:

0.250

Gnomad EAS exome

AF:

0.227

Gnomad SAS exome

AF:

0.420

Gnomad FIN exome

AF:

0.289

Gnomad NFE exome

AF:

0.273

Gnomad OTH exome

AF:

0.258

GnomAD4 exome

AF:

0.270

AC:

370338

AN:

1373446

Hom.:

52319

Cov.:

AF XY:

0.275

AC XY:

189376

AN XY:

688436

show subpopulations

Gnomad4 AFR exome

AF:

0.150

Gnomad4 AMR exome

AF:

0.145

Gnomad4 ASJ exome

AF:

0.246

Gnomad4 EAS exome

AF:

0.208

Gnomad4 SAS exome

AF:

0.421

Gnomad4 FIN exome

AF:

0.284

Gnomad4 NFE exome

AF:

0.269

Gnomad4 OTH exome

AF:

0.270

GnomAD4 genome

AF:

0.234

AC:

35669

AN:

152172

Hom.:

4505

Cov.:

AF XY:

0.236

AC XY:

17566

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.161

Gnomad4 AMR

AF:

0.173

Gnomad4 ASJ

AF:

0.246

Gnomad4 EAS

AF:

0.231

Gnomad4 SAS

AF:

0.414

Gnomad4 FIN

AF:

0.298

Gnomad4 NFE

AF:

0.270

Gnomad4 OTH

AF:

0.235

Alfa

AF:

0.263

Hom.:

11372

Bravo

AF:

0.217

Asia WGS

AF:

0.305

AC:

1062

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 07, 2018	- -

Homocystinuria due to methylene tetrahydrofolate reductase deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

2.7

DANN

Benign

0.80

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