rs11537640

Variant names:

• chr1-42958848-T-G
• rs11537640
• NM_006516.4:c.-197A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-42958848-T-G
• chr1-42958848-T-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006516.4(SLC2A1):​c.-197A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 571,510 control chromosomes in the GnomAD database, including 14,196 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4195 hom., cov: 33)
  • Exomes 𝑓: 0.21 (10001 hom.)
• Consequence: SLC2A1 NM_006516.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -1.72
• Publications: 14 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-DT (HGNC:44187): (SLC2A1 divergent transcript)

ENSG00000283973 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 1-42958848-T-G is Benign according to our data. Variant chr1-42958848-T-G is described in ClinVar as Benign. ClinVar VariationId is 297385.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.254 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.-197A>C		5_prime_UTR	Exon 1 of 10	NP_006507.2	P11166
	SLC2A1-DT	NR_033967.1		n.-201T>G		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A1	ENST00000426263.10	TSL:1 MANE Select	c.-197A>C		5_prime_UTR	Exon 1 of 10	ENSP00000416293.2	P11166
	SLC2A1	ENST00000889577.1		c.-197A>C		5_prime_UTR	Exon 1 of 10	ENSP00000559636.1
	SLC2A1	ENST00000958848.1		c.-197A>C		5_prime_UTR	Exon 1 of 10	ENSP00000628907.1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35128 AN: 151978 Hom.: 4194 Cov.: 33

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.224

GnomAD4 exome AF: 0.214 AC: 89893 AN: 419414 Hom.: 10001 Cov.: 5 AF XY: 0.213 AC XY: 47607 AN XY: 223860

African (AFR) AF: 0.260 AC: 2378 AN: 9160

American (AMR) AF: 0.237 AC: 4419 AN: 18640

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 2677 AN: 12592

East Asian (EAS) AF: 0.210 AC: 5386 AN: 25656

South Asian (SAS) AF: 0.214 AC: 9539 AN: 44638

European-Finnish (FIN) AF: 0.249 AC: 7086 AN: 28426

Middle Eastern (MID) AF: 0.196 AC: 627 AN: 3196

European-Non Finnish (NFE) AF: 0.207 AC: 52509 AN: 253272

Other (OTH) AF: 0.221 AC: 5272 AN: 23834

GnomAD4 genome AF: 0.231 AC: 35156 AN: 152096 Hom.: 4195 Cov.: 33 AF XY: 0.234 AC XY: 17415 AN XY: 74358

African (AFR) AF: 0.258 AC: 10728 AN: 41520

American (AMR) AF: 0.250 AC: 3818 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 797 AN: 3472

East Asian (EAS) AF: 0.229 AC: 1179 AN: 5142

South Asian (SAS) AF: 0.210 AC: 1009 AN: 4814

European-Finnish (FIN) AF: 0.248 AC: 2622 AN: 10584

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14299 AN: 67956

Other (OTH) AF: 0.226 AC: 476 AN: 2110

Alfa AF: 0.212 Hom.: 687

Bravo AF: 0.231

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Dystonia 9 (2)
-	-	2	Encephalopathy due to GLUT1 deficiency (2)
-	-	2	not provided (2)
-	-	1	Childhood onset GLUT1 deficiency syndrome 2 (1)
-	-	1	Epilepsy, idiopathic generalized, susceptibility to, 12 (1)
-	-	1	Hereditary cryohydrocytosis with reduced stomatin (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.6
DANN	Benign	0.60
PhyloP100		-1.7
PromoterAI		-0.17	Neutral
Mutation Taster		=300/0	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: rs11537640; hg19: chr1-43424519;