1-42943295-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.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: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
GLUT1 deficiency syndrome
Inheritance: SD, AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, ClinGen
childhood onset GLUT1 deficiency syndrome 2
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
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.

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.45C>T	p.Ala15Ala	synonymous	Exon 2 of 10	NP_006507.2	P11166

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC2A1	ENST00000426263.10	TSL:1 MANE Select	c.45C>T	p.Ala15Ala	synonymous	Exon 2 of 10	ENSP00000416293.2	P11166
SLC2A1	ENST00000889577.1		c.42C>T	p.Ala14Ala	synonymous	Exon 2 of 10	ENSP00000559636.1
SLC2A1	ENST00000958848.1		c.45C>T	p.Ala15Ala	synonymous	Exon 2 of 10	ENSP00000628907.1

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (8)

Encephalopathy due to GLUT1 deficiency (3)

Dystonia 9 (2)

not provided (2)

Childhood onset GLUT1 deficiency syndrome 2 (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

-0.51

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

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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