rs1385129

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006516.4(SLC2A1):c.45C>T(p.Ala15Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 1,611,710 control chromosomes in the GnomAD database, including 41,236 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 3828 hom., cov: 32)

Exomes 𝑓: 0.22 ( 37408 hom. )

Consequence

SLC2A1
NM_006516.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:19

Conservation

PhyloP100: -1.83

Publications

57 publications found

Variant links:

Genes affected

SLC2A1 (HGNC:11005): (solute carrier family 2 member 1) This gene encodes a major glucose transporter in the mammalian blood-brain barrier. The encoded protein is found primarily in the cell membrane and on the cell surface, where it can also function as a receptor for human T-cell leukemia virus (HTLV) I and II. Mutations in this gene have been found in a family with paroxysmal exertion-induced dyskinesia. [provided by RefSeq, Apr 2013]

SLC2A1 Gene-Disease associations (from GenCC):

encephalopathy due to GLUT1 deficiency
Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
GLUT1 deficiency syndrome
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
childhood onset GLUT1 deficiency syndrome 2
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet
dystonia 9
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
epilepsy, idiopathic generalized, susceptibility to, 12
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
childhood absence epilepsy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hereditary cryohydrocytosis with reduced stomatin
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
myoclonic-astatic epilepsy
Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

SLC2A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 1-42943295-G-A is Benign according to our data. Variant chr1-42943295-G-A is described in ClinVar as Benign. ClinVar VariationId is 95413.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.83 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A1	NM_006516.4 link	c.45C>T	p.Ala15Ala	synonymous_variant	Exon 2 of 10	ENST00000426263.10	NP_006507.2	P11166Q59GX2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC2A1	ENST00000426263.10 link	c.45C>T	p.Ala15Ala	synonymous_variant	Exon 2 of 10	1	NM_006516.4	ENSP00000416293.2		P11166

Frequencies

GnomAD3 genomes

AF:

0.219

AC:

33325

AN:

151980

Hom.:

3829

Cov.:

show subpopulations

Gnomad AFR

AF:

0.177

Gnomad AMI

AF:

0.161

Gnomad AMR

AF:

0.286

Gnomad ASJ

AF:

0.236

Gnomad EAS

AF:

0.292

Gnomad SAS

AF:

0.273

Gnomad FIN

AF:

0.243

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.216

Gnomad OTH

AF:

0.223

GnomAD2 exomes

AF:

0.242

AC:

60244

AN:

249400

AF XY:

0.242

show subpopulations

Gnomad AFR exome

AF:

0.177

Gnomad AMR exome

AF:

0.305

Gnomad ASJ exome

AF:

0.216

Gnomad EAS exome

AF:

0.288

Gnomad FIN exome

AF:

0.246

Gnomad NFE exome

AF:

0.219

Gnomad OTH exome

AF:

0.233

GnomAD4 exome

AF:

0.224

AC:

327183

AN:

1459610

Hom.:

37408

Cov.:

AF XY:

0.225

AC XY:

163661

AN XY:

726156

show subpopulations

African (AFR)

AF:

0.179

AC:

5985

AN:

33440

American (AMR)

AF:

0.303

AC:

13533

AN:

44618

Ashkenazi Jewish (ASJ)

AF:

0.217

AC:

5680

AN:

26116

East Asian (EAS)

AF:

0.254

AC:

10083

AN:

39662

South Asian (SAS)

AF:

0.270

AC:

23256

AN:

86130

European-Finnish (FIN)

AF:

0.246

AC:

13111

AN:

53296

Middle Eastern (MID)

AF:

0.222

AC:

1279

AN:

5764

European-Non Finnish (NFE)

AF:

0.217

AC:

240499

AN:

1110268

Other (OTH)

AF:

0.228

AC:

13757

AN:

60316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

12699

25398

38097

50796

63495

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8448

16896

25344

33792

42240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.219

AC:

33347

AN:

152100

Hom.:

3828

Cov.:

AF XY:

0.224

AC XY:

16659

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.177

AC:

7331

AN:

41504

American (AMR)

AF:

0.287

AC:

4382

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.236

AC:

819

AN:

3466

East Asian (EAS)

AF:

0.292

AC:

1508

AN:

5168

South Asian (SAS)

AF:

0.274

AC:

1321

AN:

4820

European-Finnish (FIN)

AF:

0.243

AC:

2569

AN:

10564

Middle Eastern (MID)

AF:

0.289

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.216

AC:

14710

AN:

67972

Other (OTH)

AF:

0.225

AC:

475

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1343

2686

4028

5371

6714

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

352

704

1056

1408

1760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.216

Hom.:

6607

Bravo

AF:

0.218

Asia WGS

AF:

0.296

AC:

1029

AN:

3478

EpiCase

AF:

0.216

EpiControl

AF:

0.212

ClinVar

Significance: Benign

Submissions summary: Benign:19

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:8

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jun 27, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 54% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 50. Only high quality variants are reported. -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Encephalopathy due to GLUT1 deficiency

Benign:3

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Apr 14, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dystonia 9

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Inborn genetic diseases

Benign:1

Mar 04, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Childhood onset GLUT1 deficiency syndrome 2

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

GLUT1 deficiency syndrome 1, autosomal recessive

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary cryohydrocytosis with reduced stomatin

Benign:1

Jul 15, 2021

Genome-Nilou Lab

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

-0.51

CADD

Benign

6.2

(source)

DANN

Benign

0.87

PhyloP100

-1.8

PromoterAI

0.023

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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

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