Variant 1-42929964-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006516.4(SLC2A1):c.588G>A(p.Pro196=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 1,613,880 control chromosomes in the GnomAD database, including 31,668 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P196P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.16 ( 2279 hom., cov: 32)

Exomes 𝑓: 0.20 ( 29389 hom. )

Consequence

SLC2A1
NM_006516.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:20

Conservation

PhyloP100: -5.43

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 1-42929964-C-T is Benign according to our data. Variant chr1-42929964-C-T is described in ClinVar as [Benign]. Clinvar id is 95414.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-42929964-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-5.43 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC2A1	NM_006516.4 linkuse as main transcript	c.588G>A	p.Pro196=	synonymous_variant	5/10	ENST00000426263.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC2A1	ENST00000426263.10 linkuse as main transcript	c.588G>A	p.Pro196=	synonymous_variant	5/10	1	NM_006516.4	P1

Frequencies

GnomAD3 genomes

AF:

0.157

AC:

23827

AN:

151950

Hom.:

2275

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0459

Gnomad AMI

AF:

0.104

Gnomad AMR

AF:

0.214

Gnomad ASJ

AF:

0.181

Gnomad EAS

AF:

0.0754

Gnomad SAS

AF:

0.174

Gnomad FIN

AF:

0.228

Gnomad MID

AF:

0.210

Gnomad NFE

AF:

0.204

Gnomad OTH

AF:

0.184

GnomAD3 exomes

AF:

0.184

AC:

46362

AN:

251344

Hom.:

4683

AF XY:

0.189

AC XY:

25702

AN XY:

135830

show subpopulations

Gnomad AFR exome

AF:

0.0418

Gnomad AMR exome

AF:

0.200

Gnomad ASJ exome

AF:

0.181

Gnomad EAS exome

AF:

0.0761

Gnomad SAS exome

AF:

0.188

Gnomad FIN exome

AF:

0.231

Gnomad NFE exome

AF:

0.208

Gnomad OTH exome

AF:

0.194

GnomAD4 exome

AF:

0.197

AC:

288354

AN:

1461812

Hom.:

29389

Cov.:

AF XY:

0.198

AC XY:

144029

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.0382

Gnomad4 AMR exome

AF:

0.203

Gnomad4 ASJ exome

AF:

0.177

Gnomad4 EAS exome

AF:

0.0803

Gnomad4 SAS exome

AF:

0.188

Gnomad4 FIN exome

AF:

0.225

Gnomad4 NFE exome

AF:

0.207

Gnomad4 OTH exome

AF:

0.184

GnomAD4 genome

AF:

0.157

AC:

23837

AN:

152068

Hom.:

2279

Cov.:

AF XY:

0.159

AC XY:

11816

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.0458

Gnomad4 AMR

AF:

0.214

Gnomad4 ASJ

AF:

0.181

Gnomad4 EAS

AF:

0.0754

Gnomad4 SAS

AF:

0.174

Gnomad4 FIN

AF:

0.228

Gnomad4 NFE

AF:

0.204

Gnomad4 OTH

AF:

0.183

Alfa

AF:

0.175

Hom.:

1927

Bravo

AF:

0.149

Asia WGS

AF:

0.117

AC:

407

AN:

3478

EpiCase

AF:

0.205

EpiControl

AF:

0.201

ClinVar

Significance: Benign

Submissions summary: Benign:20

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:9

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 15, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 40% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 37. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 27, 2016	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Encephalopathy due to GLUT1 deficiency

Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 14, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Apr 11, 2023	- -

Dystonia 9

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Apr 11, 2023	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 22, 2016

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

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

GLUT1 deficiency syndrome 1, autosomal recessive

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Hereditary cryohydrocytosis with reduced stomatin

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

Epilepsy, idiopathic generalized, susceptibility to, 12

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

7.2

DANN

Benign

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over