1-11806126-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4BA1

The ENST00000641747.1(MTHFR):n.-252G>A variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.0455 in 640,040 control chromosomes in the GnomAD database, including 792 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.037 ( 153 hom., cov: 33)

Exomes 𝑓: 0.048 ( 639 hom. )

Consequence

MTHFR
ENST00000641747.1 non_coding_transcript_exon

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.66

Publications

23 publications found

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:

CLCN6 (HGNC:2024): (chloride voltage-gated channel 6) This gene encodes a member of the voltage-dependent chloride channel protein family. Members of this family can function as either chloride channels or antiporters. This protein is primarily localized to late endosomes and functions as a chloride/proton antiporter. Alternate splicing results in both coding and non-coding variants. Additional alternately spliced variants have been described but their full-length structure is unknown. [provided by RefSeq, Mar 2012]

CLCN6 Gene-Disease associations (from GenCC):

neurodegeneration, childhood-onset, with hypotonia, respiratory insufficiency, and brain imaging abnormalities
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

CLCN6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.14).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLCN6	NM_001286.5 link	c.-137C>T		upstream_gene_variant		ENST00000346436.11	NP_001277.2	P51797-1
MTHFR	NM_005957.5 link	c.-252G>A		upstream_gene_variant		ENST00000376590.9	NP_005948.3	P42898-1Q8IU67Q59GJ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLCN6	ENST00000346436.11 link	c.-137C>T		upstream_gene_variant		1	NM_001286.5	ENSP00000234488.9		P51797-1
MTHFR	ENST00000376590.9 link	c.-252G>A		upstream_gene_variant		1	NM_005957.5	ENSP00000365775.3		P42898-1

Frequencies

GnomAD3 genomes

AF:

0.0371

AC:

5643

AN:

152200

Hom.:

151

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0110

Gnomad AMI

AF:

0.0362

Gnomad AMR

AF:

0.0404

Gnomad ASJ

AF:

0.0542

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.0423

Gnomad FIN

AF:

0.0316

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0542

Gnomad OTH

AF:

0.0416

GnomAD4 exome

AF:

0.0481

AC:

23475

AN:

487722

Hom.:

639

Cov.:

AF XY:

0.0483

AC XY:

11711

AN XY:

242544

show subpopulations

African (AFR)

AF:

0.0115

AC:

128

AN:

11146

American (AMR)

AF:

0.0339

AC:

262

AN:

7736

Ashkenazi Jewish (ASJ)

AF:

0.0506

AC:

541

AN:

10702

East Asian (EAS)

AF:

0.00583

AC:

139

AN:

23838

South Asian (SAS)

AF:

0.0380

AC:

538

AN:

14166

European-Finnish (FIN)

AF:

0.0328

AC:

1125

AN:

34314

Middle Eastern (MID)

AF:

0.115

AC:

356

AN:

3094

European-Non Finnish (NFE)

AF:

0.0538

AC:

19289

AN:

358646

Other (OTH)

AF:

0.0456

AC:

1097

AN:

24080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1161

2321

3482

4642

5803

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0371

AC:

5648

AN:

152318

Hom.:

153

Cov.:

AF XY:

0.0371

AC XY:

2762

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.0109

AC:

454

AN:

41580

American (AMR)

AF:

0.0404

AC:

618

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0542

AC:

188

AN:

3470

East Asian (EAS)

AF:

0.00174

AC:

AN:

5182

South Asian (SAS)

AF:

0.0421

AC:

203

AN:

4824

European-Finnish (FIN)

AF:

0.0316

AC:

336

AN:

10622

Middle Eastern (MID)

AF:

0.0782

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0542

AC:

3689

AN:

68018

Other (OTH)

AF:

0.0449

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

272

544

817

1089

1361

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0487

Hom.:

255

Bravo

AF:

0.0363

Asia WGS

AF:

0.0310

AC:

109

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Homocystinuria due to methylene tetrahydrofolate reductase deficiency

Benign:1

May 22, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.14

CADD

Benign

(source)

DANN

Benign

0.95

PhyloP100

3.7

PromoterAI

-0.024

Neutral

(source)

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

1-11806126-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over