rs3754219

Variant names:

• chr1-42934015-A-C
• rs3754219
• NM_006516.4:c.115-2809T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-42934015-A-C
• chr1-42934015-A-T

Variant summary

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

The NM_006516.4(SLC2A1):​c.115-2809T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 152,068 control chromosomes in the GnomAD database, including 10,828 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 0.34 (10828 hom., cov: 32)
• Consequence: SLC2A1 NM_006516.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00300
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.456 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.115-2809T>G		intron	N/A	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.115-2809T>G		intron	N/A	ENSP00000416293.2	P11166
	SLC2A1	ENST00000889577.1		c.112-2809T>G		intron	N/A	ENSP00000559636.1
	SLC2A1	ENST00000958848.1		c.115-2809T>G		intron	N/A	ENSP00000628907.1

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52191 AN: 151950 Hom.: 10827 Cov.: 32

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.621

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.368

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

GnomAD4 genome AF: 0.343 AC: 52205 AN: 152068 Hom.: 10828 Cov.: 32 AF XY: 0.342 AC XY: 25392 AN XY: 74330

African (AFR) AF: 0.100 AC: 4167 AN: 41508

American (AMR) AF: 0.329 AC: 5027 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 1466 AN: 3466

East Asian (EAS) AF: 0.374 AC: 1934 AN: 5174

South Asian (SAS) AF: 0.398 AC: 1916 AN: 4814

European-Finnish (FIN) AF: 0.465 AC: 4899 AN: 10546

Middle Eastern (MID) AF: 0.432 AC: 126 AN: 292

European-Non Finnish (NFE) AF: 0.461 AC: 31320 AN: 67976

Other (OTH) AF: 0.372 AC: 784 AN: 2108

Alfa AF: 0.415 Hom.: 17568

Bravo AF: 0.325

Asia WGS AF: 0.328 AC: 1141 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.9
DANN	Benign	0.74
PhyloP100		0.0030
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: rs3754219; hg19: chr1-43399686;