chr1-42928995-G-A

Variant names:

• chr1-42928995-G-A
• rs2229681
• NM_006516.4:c.1011C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_006516.4(SLC2A1):​c.1011C>T​(p.His337His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0148 in 1,613,778 control chromosomes in the GnomAD database, including 2,452 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.071 (1279 hom., cov: 33)
  • Exomes 𝑓: 0.0088 (1173 hom.)
• Consequence: SLC2A1 NM_006516.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:18
• Conservation: PhyloP100: 3.27
• Publications: 9 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 1-42928995-G-A is Benign according to our data. Variant chr1-42928995-G-A is described in ClinVar as Benign. ClinVar VariationId is 95406.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=3.27 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.24 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.1011C>T	p.His337His	synonymous	Exon 8 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.1011C>T	p.His337His	synonymous	Exon 8 of 10	ENSP00000416293.2	P11166
	SLC2A1	ENST00000889577.1		c.1008C>T	p.His336His	synonymous	Exon 8 of 10	ENSP00000559636.1
	SLC2A1	ENST00000958848.1		c.1011C>T	p.His337His	synonymous	Exon 8 of 10	ENSP00000628907.1

Frequencies

GnomAD3 genomes AF: 0.0711 AC: 10824 AN: 152198 Hom.: 1265 Cov.: 33

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0276

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.0281

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000896

Gnomad OTH AF: 0.0488

GnomAD2 exomes AF: 0.0214 AC: 5365 AN: 250780 AF XY: 0.0175

Gnomad AFR exome AF: 0.246

Gnomad AMR exome AF: 0.0131

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00435

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000758

Gnomad OTH exome AF: 0.0109

GnomAD4 exome AF: 0.00885 AC: 12931 AN: 1461462 Hom.: 1173 Cov.: 32 AF XY: 0.00843 AC XY: 6129 AN XY: 727090

African (AFR) AF: 0.253 AC: 8466 AN: 33470

American (AMR) AF: 0.0143 AC: 640 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00191 AC: 76 AN: 39700

South Asian (SAS) AF: 0.0229 AC: 1973 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53018

Middle Eastern (MID) AF: 0.0160 AC: 92 AN: 5768

European-Non Finnish (NFE) AF: 0.000487 AC: 542 AN: 1111998

Other (OTH) AF: 0.0189 AC: 1141 AN: 60390

GnomAD4 genome AF: 0.0715 AC: 10885 AN: 152316 Hom.: 1279 Cov.: 33 AF XY: 0.0694 AC XY: 5169 AN XY: 74486

African (AFR) AF: 0.244 AC: 10151 AN: 41542

American (AMR) AF: 0.0276 AC: 422 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00251 AC: 13 AN: 5182

South Asian (SAS) AF: 0.0275 AC: 133 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000897 AC: 61 AN: 68036

Other (OTH) AF: 0.0482 AC: 102 AN: 2114

Alfa AF: 0.0264 Hom.: 250

Bravo AF: 0.0793

Asia WGS AF: 0.0290 AC: 102 AN: 3478

EpiCase AF: 0.000545

EpiControl AF: 0.00119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	8	not specified (8)
-	-	2	Dystonia 9 (2)
-	-	2	Encephalopathy due to GLUT1 deficiency (2)
-	-	1	Childhood onset GLUT1 deficiency syndrome 2 (1)
-	-	1	Epilepsy, idiopathic generalized, susceptibility to, 12 (1)
-	-	1	GLUT1 deficiency syndrome 1, autosomal recessive (1)
-	-	1	Hereditary cryohydrocytosis with reduced stomatin (1)
-	-	1	Inborn genetic diseases (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	9.4
DANN	Benign	0.91
PhyloP100		3.3
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
Mutation Taster		=96/4	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: rs2229681; hg19: chr1-43394666;