1-42933496-G-T

Variant names:

• chr1-42933496-G-T
• rs841858
• NM_006516.4:c.115-2290C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006516.4(SLC2A1):​c.115-2290C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,144 control chromosomes in the GnomAD database, including 2,273 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2273 hom., cov: 31)
• Consequence: SLC2A1 NM_006516.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780
• Publications: 12 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: 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: Genomics England PanelApp, Orphanet
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A1	NM_006516.4	c.115-2290C>A		intron_variant	Intron 2 of 9	ENST00000426263.10	NP_006507.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC2A1	ENST00000426263.10	c.115-2290C>A		intron_variant	Intron 2 of 9	1	NM_006516.4	ENSP00000416293.2

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25315 AN: 152026 Hom.: 2270 Cov.: 31

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.176

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.167 AC: 25334 AN: 152144 Hom.: 2273 Cov.: 31 AF XY: 0.169 AC XY: 12535 AN XY: 74378

African (AFR) AF: 0.120 AC: 4993 AN: 41504

American (AMR) AF: 0.214 AC: 3263 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 557 AN: 3472

East Asian (EAS) AF: 0.185 AC: 955 AN: 5168

South Asian (SAS) AF: 0.180 AC: 869 AN: 4834

European-Finnish (FIN) AF: 0.182 AC: 1926 AN: 10590

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12251 AN: 67988

Other (OTH) AF: 0.177 AC: 374 AN: 2110

Alfa AF: 0.172 Hom.: 3899

Bravo AF: 0.164

Asia WGS AF: 0.186 AC: 648 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.4
DANN	Benign	0.71
PhyloP100		-0.078
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: rs841858; hg19: chr1-43399167;