rs146879902

chr1-42927083-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_006516.4(SLC2A1):c.1437C>T(p.Pro479=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000743 in 1,614,140 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00062 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00076 (1 hom.)
• Consequence: SLC2A1 NM_006516.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:14
• Conservation: PhyloP100: -5.16

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 1-42927083-G-A is Benign according to our data. Variant chr1-42927083-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 139168.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.16 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC2A1	NM_006516.4	c.1437C>T	p.Pro479=	synonymous_variant	10/10	ENST00000426263.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC2A1	ENST00000426263.10	c.1437C>T	p.Pro479=	synonymous_variant	10/10	1	NM_006516.4	P1

Frequencies

GnomAD3 genomes AF: 0.000624 AC: 95 AN: 152136 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000882

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000561 AC: 141 AN: 251340 Hom.: 0 AF XY: 0.000537 AC XY: 73 AN XY: 135852

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000781

Gnomad ASJ exome AF: 0.00159

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.000775

Gnomad OTH exome AF: 0.000651

GnomAD4 exome AF: 0.000755 AC: 1104 AN: 1461886 Hom.: 1 Cov.: 32 AF XY: 0.000715 AC XY: 520 AN XY: 727242

Gnomad4 AFR exome AF: 0.000149

Gnomad4 AMR exome AF: 0.000850

Gnomad4 ASJ exome AF: 0.00172

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.000879

Gnomad4 OTH exome AF: 0.000580

GnomAD4 genome AF: 0.000624 AC: 95 AN: 152254 Hom.: 0 Cov.: 32 AF XY: 0.000618 AC XY: 46 AN XY: 74446

Gnomad4 AFR AF: 0.000265

Gnomad4 AMR AF: 0.00124

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000882

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000884 Hom.: 0

Bravo AF: 0.000669

EpiCase AF: 0.000763

EpiControl AF: 0.000830

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:14

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 16, 2014	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. -
Likely benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 26, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Dec 21, 2016	- -
Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Jan 31, 2019	- -

Dystonia 9 Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Apr 11, 2023	- -
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. -

Encephalopathy due to GLUT1 deficiency Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Apr 11, 2023	- -
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. -

Inborn genetic diseases Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 21, 2017

This alteration is classified as likely 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

Likely benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2023

SLC2A1: BP4, BP7 -

GLUT1 deficiency syndrome 1, autosomal recessive Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 10, 2024

- -

Hereditary cryohydrocytosis with reduced stomatin Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

Epilepsy, idiopathic generalized, susceptibility to, 12 Benign:1

Likely 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	-0.83
Cadd	Benign	0.42
Dann	Benign	0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

LitVar

Other links and lift over

dbSNP: rs146879902; hg19: chr1-43392754; COSMIC: COSV65287592; COSMIC: COSV65287592;