1-42929866-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_006516.4(SLC2A1):c.679+7G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00144 in 1,614,092 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0014 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 38 hom. )

Consequence

SLC2A1
NM_006516.4 splice_region, intron

Scores

Splicing: ADA: 0.001765

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.445

Publications

4 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 1-42929866-C-A is Benign according to our data. Variant chr1-42929866-C-A is described in ClinVar as Benign. ClinVar VariationId is 139161.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00139 (211/152224) while in subpopulation EAS AF = 0.035 (181/5178). AF 95% confidence interval is 0.0308. There are 5 homozygotes in GnomAd4. There are 108 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 AD,AR,Unknown gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A1	NM_006516.4	MANE Select	c.679+7G>T		splice_region intron	N/A	NP_006507.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SLC2A1	ENST00000426263.10	TSL:1 MANE Select	c.679+7G>T	splice_region intron	N/A	ENSP00000416293.2
SLC2A1	ENST00000674765.1		c.679+7G>T	splice_region intron	N/A	ENSP00000501811.1
SLC2A1	ENST00000475162.3	TSL:5	c.414+760G>T	intron	N/A	ENSP00000487213.1

Frequencies

GnomAD3 genomes

AF:

0.00139

AC:

211

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.0349

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.00301

AC:

757

AN:

251440

AF XY:

0.00275

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00129

Gnomad EAS exome

AF:

0.0371

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000149

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00144

AC:

2112

AN:

1461868

Hom.:

Cov.:

AF XY:

0.00142

AC XY:

1031

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000447

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00168

AC:

AN:

26134

East Asian (EAS)

AF:

0.0447

AC:

1776

AN:

39700

South Asian (SAS)

AF:

0.000858

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000809

AC:

AN:

1111992

Other (OTH)

AF:

0.00205

AC:

124

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

153

305

458

610

763

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<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:

0.00139

AC:

211

AN:

152224

Hom.:

Cov.:

AF XY:

0.00145

AC XY:

108

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41524

American (AMR)

AF:

0.000262

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3470

East Asian (EAS)

AF:

0.0350

AC:

181

AN:

5178

South Asian (SAS)

AF:

0.00166

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

68004

Other (OTH)

AF:

0.000474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000506

Hom.:

Bravo

AF:

0.00155

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Oct 18, 2012

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Sep 03, 2015

Eurofins Ntd Llc (ga)

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

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 11, 2023

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Encephalopathy due to GLUT1 deficiency

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Apr 11, 2023

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Childhood onset GLUT1 deficiency syndrome 2

Benign:1

Apr 11, 2023

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

GLUT1 deficiency syndrome 1, autosomal recessive

Benign:1

Feb 02, 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

Apr 11, 2023

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Epilepsy, idiopathic generalized, susceptibility to, 12

Benign:1

Apr 11, 2023

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

0.45

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0018

dbscSNV1_RF

Benign

0.12

SpliceAI score (max)

0.020

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over