rs16830101

Variant names:

• chr1-42942899-C-G
• rs16830101
• NM_006516.4:c.114+327G>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.114+327G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0981 in 385,920 control chromosomes in the GnomAD database, including 2,208 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 0.090 (783 hom., cov: 31)
  • Exomes 𝑓: 0.10 (1425 hom.)
• Consequence: SLC2A1 NM_006516.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.781
• Publications: 2 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A1	NM_006516.4	c.114+327G>C		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.114+327G>C		intron_variant	Intron 2 of 9	1	NM_006516.4	ENSP00000416293.2

Frequencies

GnomAD3 genomes AF: 0.0900 AC: 13687 AN: 152032 Hom.: 780 Cov.: 31

Gnomad AFR AF: 0.0421

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.0985

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.0779

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0965

Gnomad OTH AF: 0.0915

GnomAD4 exome AF: 0.103 AC: 24137 AN: 233770 Hom.: 1425 AF XY: 0.107 AC XY: 13445 AN XY: 125912

African (AFR) AF: 0.0372 AC: 260 AN: 6984

American (AMR) AF: 0.167 AC: 1873 AN: 11238

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 705 AN: 6406

East Asian (EAS) AF: 0.132 AC: 1546 AN: 11746

South Asian (SAS) AF: 0.138 AC: 5384 AN: 39156

European-Finnish (FIN) AF: 0.0717 AC: 746 AN: 10398

Middle Eastern (MID) AF: 0.0879 AC: 80 AN: 910

European-Non Finnish (NFE) AF: 0.0920 AC: 12370 AN: 134394

Other (OTH) AF: 0.0936 AC: 1173 AN: 12538

GnomAD4 genome AF: 0.0901 AC: 13706 AN: 152150 Hom.: 783 Cov.: 31 AF XY: 0.0928 AC XY: 6902 AN XY: 74364

African (AFR) AF: 0.0423 AC: 1757 AN: 41508

American (AMR) AF: 0.168 AC: 2574 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0985 AC: 342 AN: 3472

East Asian (EAS) AF: 0.122 AC: 633 AN: 5180

South Asian (SAS) AF: 0.139 AC: 667 AN: 4806

European-Finnish (FIN) AF: 0.0779 AC: 824 AN: 10580

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0965 AC: 6564 AN: 68010

Other (OTH) AF: 0.0900 AC: 190 AN: 2110

Alfa AF: 0.0939 Hom.: 74

Bravo AF: 0.0932

Asia WGS AF: 0.106 AC: 369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.9
DANN	Benign	0.67
PhyloP100		0.78
PromoterAI		0.0086	Neutral
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: rs16830101; hg19: chr1-43408570;