chr1-42930743-G-A

Variant names:

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.399C>T(p.Cys133Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,609,076 control chromosomes in the GnomAD database, including 30,999 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2440 hom., cov: 32)

Exomes 𝑓: 0.20 ( 28559 hom. )

Consequence

SLC2A1
NM_006516.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:22

Conservation

PhyloP100: -1.50

Publications

21 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=-0.59).

BP6

Variant 1-42930743-G-A is Benign according to our data. Variant chr1-42930743-G-A is described in ClinVar as Benign. ClinVar VariationId is 95411.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.5 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006516.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A1	NM_006516.4	MANE Select	c.399C>T	p.Cys133Cys	synonymous	Exon 4 of 10	NP_006507.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC2A1	ENST00000426263.10	TSL:1 MANE Select	c.399C>T	p.Cys133Cys	synonymous	Exon 4 of 10	ENSP00000416293.2
SLC2A1	ENST00000889577.1		c.396C>T	p.Cys132Cys	synonymous	Exon 4 of 10	ENSP00000559636.1
SLC2A1	ENST00000958848.1		c.399C>T	p.Cys133Cys	synonymous	Exon 4 of 10	ENSP00000628907.1

Frequencies

GnomAD3 genomes

AF:

0.170

AC:

25905

AN:

152052

Hom.:

2436

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0941

Gnomad AMI

AF:

0.104

Gnomad AMR

AF:

0.220

Gnomad ASJ

AF:

0.187

Gnomad EAS

AF:

0.0991

Gnomad SAS

AF:

0.187

Gnomad FIN

AF:

0.225

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.201

Gnomad OTH

AF:

0.187

GnomAD2 exomes

AF:

0.190

AC:

46816

AN:

246772

AF XY:

0.194

show subpopulations

Gnomad AFR exome

AF:

0.0925

Gnomad AMR exome

AF:

0.203

Gnomad ASJ exome

AF:

0.184

Gnomad EAS exome

AF:

0.0999

Gnomad FIN exome

AF:

0.234

Gnomad NFE exome

AF:

0.205

Gnomad OTH exome

AF:

0.200

GnomAD4 exome

AF:

0.196

AC:

285607

AN:

1456906

Hom.:

28559

Cov.:

AF XY:

0.197

AC XY:

142748

AN XY:

725080

show subpopulations

African (AFR)

AF:

0.0901

AC:

3015

AN:

33478

American (AMR)

AF:

0.206

AC:

9226

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.182

AC:

4748

AN:

26136

East Asian (EAS)

AF:

0.0917

AC:

3641

AN:

39694

South Asian (SAS)

AF:

0.198

AC:

17107

AN:

86250

European-Finnish (FIN)

AF:

0.222

AC:

10811

AN:

48678

Middle Eastern (MID)

AF:

0.187

AC:

1076

AN:

5768

European-Non Finnish (NFE)

AF:

0.202

AC:

224656

AN:

1111844

Other (OTH)

AF:

0.188

AC:

11327

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

14663

29326

43989

58652

73315

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7742

15484

23226

30968

38710

<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:

0.170

AC:

25920

AN:

152170

Hom.:

2440

Cov.:

AF XY:

0.173

AC XY:

12844

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.0939

AC:

3901

AN:

41528

American (AMR)

AF:

0.221

AC:

3377

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.187

AC:

649

AN:

3472

East Asian (EAS)

AF:

0.0991

AC:

513

AN:

5176

South Asian (SAS)

AF:

0.188

AC:

907

AN:

4824

European-Finnish (FIN)

AF:

0.225

AC:

2386

AN:

10582

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.201

AC:

13632

AN:

67972

Other (OTH)

AF:

0.187

AC:

394

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1140

2281

3421

4562

5702

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

288

576

864

1152

1440

<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:

0.187

Hom.:

1733

Bravo

AF:

0.164

Asia WGS

AF:

0.141

AC:

492

AN:

3478

EpiCase

AF:

0.202

EpiControl

AF:

0.198

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (10)

not provided (3)

Dystonia 9 (2)

Encephalopathy due to GLUT1 deficiency (2)

Childhood onset GLUT1 deficiency syndrome 2 (1)

Epilepsy, idiopathic generalized, susceptibility to, 12 (1)

GLUT1 deficiency syndrome 1, autosomal recessive (1)

Hereditary cryohydrocytosis with reduced stomatin (1)

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

5.6

(source)

DANN

Benign

0.87

PhyloP100

-1.5

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)

0.050

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over