rs4658

Variant names:

• chr1-42926579-C-G
• rs4658
• NM_006516.4:c.*462G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-42926579-C-G
• chr1-42926579-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006516.4(SLC2A1):​c.*462G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 595,632 control chromosomes in the GnomAD database, including 24,313 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (10919 hom., cov: 32)
  • Exomes 𝑓: 0.23 (13394 hom.)
• Consequence: SLC2A1 NM_006516.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.308
• Publications: 26 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 1-42926579-C-G is Benign according to our data. Variant chr1-42926579-C-G is described in ClinVar as Benign. ClinVar VariationId is 297374.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.585 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.*462G>C		3_prime_UTR	Exon 10 of 10	NP_006507.2	P11166

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A1	ENST00000426263.10	TSL:1 MANE Select	c.*462G>C		3_prime_UTR	Exon 10 of 10	ENSP00000416293.2	P11166
	SLC2A1	ENST00000889577.1		c.*462G>C		3_prime_UTR	Exon 10 of 10	ENSP00000559636.1
	SLC2A1	ENST00000958848.1		c.*462G>C		3_prime_UTR	Exon 10 of 10	ENSP00000628907.1

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51840 AN: 151984 Hom.: 10880 Cov.: 32

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.308

GnomAD4 exome AF: 0.235 AC: 104080 AN: 443528 Hom.: 13394 Cov.: 7 AF XY: 0.235 AC XY: 53402 AN XY: 227240

African (AFR) AF: 0.598 AC: 5964 AN: 9978

American (AMR) AF: 0.370 AC: 5659 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 1265 AN: 6614

East Asian (EAS) AF: 0.319 AC: 2849 AN: 8926

South Asian (SAS) AF: 0.257 AC: 12165 AN: 47426

European-Finnish (FIN) AF: 0.236 AC: 2102 AN: 8902

Middle Eastern (MID) AF: 0.227 AC: 599 AN: 2636

European-Non Finnish (NFE) AF: 0.212 AC: 69260 AN: 326372

Other (OTH) AF: 0.243 AC: 4217 AN: 17366

GnomAD4 genome AF: 0.342 AC: 51949 AN: 152104 Hom.: 10919 Cov.: 32 AF XY: 0.342 AC XY: 25458 AN XY: 74340

African (AFR) AF: 0.591 AC: 24528 AN: 41488

American (AMR) AF: 0.364 AC: 5558 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 698 AN: 3466

East Asian (EAS) AF: 0.313 AC: 1614 AN: 5158

South Asian (SAS) AF: 0.266 AC: 1282 AN: 4820

European-Finnish (FIN) AF: 0.246 AC: 2606 AN: 10584

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14837 AN: 67990

Other (OTH) AF: 0.307 AC: 649 AN: 2116

Alfa AF: 0.137 Hom.: 237

Bravo AF: 0.359

Asia WGS AF: 0.321 AC: 1117 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Dystonia 9 (1)
-	-	1	Encephalopathy due to GLUT1 deficiency (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.5
DANN	Benign	0.38
PhyloP100		-0.31
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4658; hg19: chr1-43392250; COSMIC: COSV107471427; COSMIC: COSV107471427;