chr1-42937037-T-C

Variant names:

• chr1-42937037-T-C
• rs841847
• NM_006516.4:c.115-5831A>G

Variant summary

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

The NM_006516.4(SLC2A1):​c.115-5831A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 152,110 control chromosomes in the GnomAD database, including 50,681 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 0.81 (50681 hom., cov: 32)
• Consequence: SLC2A1 NM_006516.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• Publications: 11 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.931 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.115-5831A>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.115-5831A>G		intron	N/A	ENSP00000416293.2	P11166
	SLC2A1	ENST00000889577.1		c.112-5831A>G		intron	N/A	ENSP00000559636.1
	SLC2A1	ENST00000958848.1		c.115-5831A>G		intron	N/A	ENSP00000628907.1

Frequencies

GnomAD3 genomes AF: 0.812 AC: 123392 AN: 151992 Hom.: 50607 Cov.: 32

Gnomad AFR AF: 0.939

Gnomad AMI AF: 0.862

Gnomad AMR AF: 0.760

Gnomad ASJ AF: 0.722

Gnomad EAS AF: 0.876

Gnomad SAS AF: 0.810

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.788

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

GnomAD4 genome AF: 0.812 AC: 123528 AN: 152110 Hom.: 50681 Cov.: 32 AF XY: 0.812 AC XY: 60366 AN XY: 74358

African (AFR) AF: 0.939 AC: 38968 AN: 41508

American (AMR) AF: 0.760 AC: 11607 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.722 AC: 2505 AN: 3470

East Asian (EAS) AF: 0.876 AC: 4496 AN: 5132

South Asian (SAS) AF: 0.811 AC: 3907 AN: 4816

European-Finnish (FIN) AF: 0.780 AC: 8260 AN: 10594

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.752 AC: 51103 AN: 67998

Other (OTH) AF: 0.791 AC: 1667 AN: 2108

Alfa AF: 0.762 Hom.: 22448

Bravo AF: 0.814

Asia WGS AF: 0.861 AC: 2994 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.18
DANN	Benign	0.75
PhyloP100		-1.4
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: rs841847; hg19: chr1-43402708;