rs28365848

Variant names:

• chr1-42959040-CT-C
• rs28365848
• ENST00000416689.3:n.10delT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The ENST00000416689.3(SLC2A1-DT):​n.10delT variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 220,588 control chromosomes in the GnomAD database, including 5,620 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4176 hom., cov: 26)
  • Exomes 𝑓: 0.19 (1444 hom.)
• Consequence: SLC2A1-DT ENST00000416689.3 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.718
• Publications: 3 publications found

Genes affected

SLC2A1-DT (HGNC:44187): (SLC2A1 divergent transcript)

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: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
• GLUT1 deficiency syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: 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: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet
• 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

ENSG00000283973 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 1-42959040-CT-C is Benign according to our data. Variant chr1-42959040-CT-C is described in ClinVar as Benign. ClinVar VariationId is 297392.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000416689.3. 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.-390delA		upstream_gene	N/A	NP_006507.2	P11166
	SLC2A1-DT	NR_033967.1		n.-8delT		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A1-DT	ENST00000416689.3	TSL:2	n.10delT		non_coding_transcript_exon	Exon 1 of 3
	SLC2A1-DT	ENST00000755359.1		n.14delT		non_coding_transcript_exon	Exon 1 of 4
	SLC2A1	ENST00000426263.10	TSL:1 MANE Select	c.-390delA		upstream_gene	N/A	ENSP00000416293.2	P11166

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35091 AN: 151988 Hom.: 4175 Cov.: 26

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.223

GnomAD4 exome AF: 0.190 AC: 13033 AN: 68482 Hom.: 1444 Cov.: 0 AF XY: 0.191 AC XY: 7055 AN XY: 36914

African (AFR) AF: 0.227 AC: 378 AN: 1668

American (AMR) AF: 0.204 AC: 374 AN: 1830

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 446 AN: 2290

East Asian (EAS) AF: 0.180 AC: 787 AN: 4362

South Asian (SAS) AF: 0.202 AC: 1658 AN: 8204

European-Finnish (FIN) AF: 0.208 AC: 728 AN: 3496

Middle Eastern (MID) AF: 0.201 AC: 66 AN: 328

European-Non Finnish (NFE) AF: 0.185 AC: 7829 AN: 42280

Other (OTH) AF: 0.191 AC: 767 AN: 4024

GnomAD4 genome AF: 0.231 AC: 35119 AN: 152106 Hom.: 4176 Cov.: 26 AF XY: 0.234 AC XY: 17403 AN XY: 74350

African (AFR) AF: 0.258 AC: 10702 AN: 41490

American (AMR) AF: 0.249 AC: 3815 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 797 AN: 3468

East Asian (EAS) AF: 0.228 AC: 1177 AN: 5152

South Asian (SAS) AF: 0.209 AC: 1008 AN: 4828

European-Finnish (FIN) AF: 0.247 AC: 2623 AN: 10600

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14294 AN: 67960

Other (OTH) AF: 0.225 AC: 475 AN: 2112

Alfa AF: 0.0646 Hom.: 138

Bravo AF: 0.230

Asia WGS AF: 0.243 AC: 845 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Childhood onset GLUT1 deficiency syndrome 2 (1)
-	-	1	Dystonia 9 (1)
-	-	1	Dystonic disorder (1)
-	-	1	Encephalopathy due to GLUT1 deficiency (1)
-	-	1	Epilepsy, idiopathic generalized, susceptibility to, 12 (1)
-	-	1	GLUT1 deficiency syndrome (1)
-	-	1	Hereditary cryohydrocytosis with reduced stomatin (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.72
Mutation Taster		=100/0	polymorphism

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: rs28365848; hg19: chr1-43424711;