1-42929964-C-T

Variant names:

• chr1-42929964-C-T
• rs2229682
• NM_006516.4:c.588G>A

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.588G>A​(p.Pro196Pro) 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 Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.16 (2279 hom., cov: 32)
  • Exomes 𝑓: 0.20 (29389 hom.)
• Consequence: SLC2A1 NM_006516.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:21
• Conservation: PhyloP100: -5.43
• Publications: 23 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=-0.57).
• BP6: Variant 1-42929964-C-T is Benign according to our data. Variant chr1-42929964-C-T is described in ClinVar as Benign. ClinVar VariationId is 95414.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

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.588G>A	p.Pro196Pro	synonymous	Exon 5 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.588G>A	p.Pro196Pro	synonymous	Exon 5 of 10	ENSP00000416293.2	P11166
	SLC2A1	ENST00000889577.1		c.585G>A	p.Pro195Pro	synonymous	Exon 5 of 10	ENSP00000559636.1
	SLC2A1	ENST00000958848.1		c.588G>A	p.Pro196Pro	synonymous	Exon 5 of 10	ENSP00000628907.1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23827 AN: 151950 Hom.: 2275 Cov.: 32

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

GnomAD2 exomes AF: 0.184 AC: 46362 AN: 251344 AF XY: 0.189

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 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.: 35 AF XY: 0.198 AC XY: 144029 AN XY: 727210

African (AFR) AF: 0.0382 AC: 1278 AN: 33480

American (AMR) AF: 0.203 AC: 9068 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 4632 AN: 26134

East Asian (EAS) AF: 0.0803 AC: 3187 AN: 39700

South Asian (SAS) AF: 0.188 AC: 16236 AN: 86256

European-Finnish (FIN) AF: 0.225 AC: 11994 AN: 53416

Middle Eastern (MID) AF: 0.182 AC: 1050 AN: 5766

European-Non Finnish (NFE) AF: 0.207 AC: 229774 AN: 1111944

Other (OTH) AF: 0.184 AC: 11135 AN: 60392

GnomAD4 genome AF: 0.157 AC: 23837 AN: 152068 Hom.: 2279 Cov.: 32 AF XY: 0.159 AC XY: 11816 AN XY: 74318

African (AFR) AF: 0.0458 AC: 1901 AN: 41508

American (AMR) AF: 0.214 AC: 3271 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 628 AN: 3464

East Asian (EAS) AF: 0.0754 AC: 390 AN: 5172

South Asian (SAS) AF: 0.174 AC: 840 AN: 4816

European-Finnish (FIN) AF: 0.228 AC: 2415 AN: 10572

Middle Eastern (MID) AF: 0.216 AC: 63 AN: 292

European-Non Finnish (NFE) AF: 0.204 AC: 13848 AN: 67956

Other (OTH) AF: 0.183 AC: 386 AN: 2104

Alfa AF: 0.174 Hom.: 2495

Bravo AF: 0.149

Asia WGS AF: 0.117 AC: 407 AN: 3478

EpiCase AF: 0.205

EpiControl AF: 0.201

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	9	not specified (9)
-	-	3	Encephalopathy due to GLUT1 deficiency (3)
-	-	2	Dystonia 9 (2)
-	-	2	not provided (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)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	7.2
DANN	Benign	0.88
PhyloP100		-5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2229682; hg19: chr1-43395635; COSMIC: COSV65286860; COSMIC: COSV65286860;