1-42951479-T-G

Variant names:

• chr1-42951479-T-G
• rs4660691
• NM_006516.4:c.18+7155A>C

Variant summary

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

The NM_006516.4(SLC2A1):​c.18+7155A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 182,138 control chromosomes in the GnomAD database, including 52,843 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 0.76 (43593 hom., cov: 31)
  • Exomes 𝑓: 0.78 (9250 hom.)
• Consequence: SLC2A1 NM_006516.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.437
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.784 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.18+7155A>C		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.18+7155A>C		intron	N/A	ENSP00000416293.2	P11166
	SLC2A1	ENST00000889577.1		c.18+7155A>C		intron	N/A	ENSP00000559636.1
	SLC2A1	ENST00000958848.1		c.18+7155A>C		intron	N/A	ENSP00000628907.1

Frequencies

GnomAD3 genomes AF: 0.755 AC: 114742 AN: 151960 Hom.: 43564 Cov.: 31

Gnomad AFR AF: 0.693

Gnomad AMI AF: 0.839

Gnomad AMR AF: 0.746

Gnomad ASJ AF: 0.771

Gnomad EAS AF: 0.771

Gnomad SAS AF: 0.791

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.789

Gnomad OTH AF: 0.766

GnomAD4 exome AF: 0.783 AC: 23526 AN: 30060 Hom.: 9250 AF XY: 0.787 AC XY: 11927 AN XY: 15154

African (AFR) AF: 0.681 AC: 904 AN: 1328

American (AMR) AF: 0.761 AC: 642 AN: 844

Ashkenazi Jewish (ASJ) AF: 0.772 AC: 1145 AN: 1484

East Asian (EAS) AF: 0.798 AC: 1822 AN: 2284

South Asian (SAS) AF: 0.765 AC: 202 AN: 264

European-Finnish (FIN) AF: 0.735 AC: 863 AN: 1174

Middle Eastern (MID) AF: 0.823 AC: 135 AN: 164

European-Non Finnish (NFE) AF: 0.793 AC: 16075 AN: 20268

Other (OTH) AF: 0.772 AC: 1738 AN: 2250

GnomAD4 genome AF: 0.755 AC: 114830 AN: 152078 Hom.: 43593 Cov.: 31 AF XY: 0.752 AC XY: 55934 AN XY: 74338

African (AFR) AF: 0.694 AC: 28750 AN: 41454

American (AMR) AF: 0.746 AC: 11388 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.771 AC: 2674 AN: 3470

East Asian (EAS) AF: 0.771 AC: 3979 AN: 5160

South Asian (SAS) AF: 0.790 AC: 3812 AN: 4824

European-Finnish (FIN) AF: 0.752 AC: 7952 AN: 10578

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.789 AC: 53679 AN: 68002

Other (OTH) AF: 0.765 AC: 1617 AN: 2114

Alfa AF: 0.784 Hom.: 22714

Bravo AF: 0.753

Asia WGS AF: 0.753 AC: 2618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.5
DANN	Benign	0.66
PhyloP100		0.44
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: rs4660691; hg19: chr1-43417150;