NM_006516.4:c.-197A>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006516.4(SLC2A1):c.-197A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 571,510 control chromosomes in the GnomAD database, including 14,196 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4195 hom., cov: 33)

Exomes 𝑓: 0.21 ( 10001 hom. )

Consequence

SLC2A1
NM_006516.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -1.72

Publications

14 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 links:

SLC2A1-DT (HGNC:44187): (SLC2A1 divergent transcript)

SLC2A1-DT links:

ENSG00000283973 (HGNC:):

ENSG00000283973 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=-0.77).

BP6

Variant 1-42958848-T-G is Benign according to our data. Variant chr1-42958848-T-G is described in ClinVar as Benign. ClinVar VariationId is 297385.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A1	NM_006516.4 link	c.-197A>C		5_prime_UTR_variant	Exon 1 of 10	ENST00000426263.10	NP_006507.2	P11166Q59GX2
SLC2A1-DT	NR_033967.1 link	n.-201T>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC2A1	ENST00000426263.10 link	c.-197A>C		5_prime_UTR_variant	Exon 1 of 10	1	NM_006516.4	ENSP00000416293.2		P11166

Frequencies

GnomAD3 genomes

AF:

0.231

AC:

35128

AN:

151978

Hom.:

4194

Cov.:

show subpopulations

Gnomad AFR

AF:

0.259

Gnomad AMI

AF:

0.161

Gnomad AMR

AF:

0.249

Gnomad ASJ

AF:

0.230

Gnomad EAS

AF:

0.230

Gnomad SAS

AF:

0.209

Gnomad FIN

AF:

0.248

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.210

Gnomad OTH

AF:

0.224

GnomAD4 exome

AF:

0.214

AC:

89893

AN:

419414

Hom.:

10001

Cov.:

AF XY:

0.213

AC XY:

47607

AN XY:

223860

show subpopulations

African (AFR)

AF:

0.260

AC:

2378

AN:

9160

American (AMR)

AF:

0.237

AC:

4419

AN:

18640

Ashkenazi Jewish (ASJ)

AF:

0.213

AC:

2677

AN:

12592

East Asian (EAS)

AF:

0.210

AC:

5386

AN:

25656

South Asian (SAS)

AF:

0.214

AC:

9539

AN:

44638

European-Finnish (FIN)

AF:

0.249

AC:

7086

AN:

28426

Middle Eastern (MID)

AF:

0.196

AC:

627

AN:

3196

European-Non Finnish (NFE)

AF:

0.207

AC:

52509

AN:

253272

Other (OTH)

AF:

0.221

AC:

5272

AN:

23834

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

3334

6669

10003

13338

16672

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

374

748

1122

1496

1870

<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:

0.231

AC:

35156

AN:

152096

Hom.:

4195

Cov.:

AF XY:

0.234

AC XY:

17415

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.258

AC:

10728

AN:

41520

American (AMR)

AF:

0.250

AC:

3818

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.230

AC:

797

AN:

3472

East Asian (EAS)

AF:

0.229

AC:

1179

AN:

5142

South Asian (SAS)

AF:

0.210

AC:

1009

AN:

4814

European-Finnish (FIN)

AF:

0.248

AC:

2622

AN:

10584

Middle Eastern (MID)

AF:

0.276

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.210

AC:

14299

AN:

67956

Other (OTH)

AF:

0.226

AC:

476

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1429

2858

4288

5717

7146

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

360

720

1080

1440

1800

<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:

0.212

Hom.:

687

Bravo

AF:

0.231

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Dystonia 9

Benign:2

Apr 11, 2023

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 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. -

Encephalopathy due to GLUT1 deficiency

Benign:2

Jan 12, 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

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 14, 2018

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. -

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

- -

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

5.6

(source)

DANN

Benign

0.60

PhyloP100

-1.7

PromoterAI

-0.17

Neutral

(source)

Mutation Taster

=300/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over