rs75485205

Variant names:

• chr1-42927224-G-A
• rs75485205
• NM_006516.4:c.1296C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-42927224-G-A
• chr1-42927224-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_006516.4(SLC2A1):​c.1296C>T​(p.Tyr432Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000562 in 1,614,042 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0025 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00036 (2 hom.)
• Consequence: SLC2A1 NM_006516.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:13
• Conservation: PhyloP100: -1.77
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 1-42927224-G-A is Benign according to our data. Variant chr1-42927224-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 95408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.77 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00248 (378/152342) while in subpopulation AFR AF = 0.00818 (340/41580). AF 95% confidence interval is 0.00746. There are 2 homozygotes in GnomAd4. There are 189 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AD,AR,Unknown gene

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.1296C>T	p.Tyr432Tyr	synonymous	Exon 10 of 10	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.1296C>T	p.Tyr432Tyr	synonymous	Exon 10 of 10	ENSP00000416293.2	P11166
	SLC2A1	ENST00000889577.1		c.1293C>T	p.Tyr431Tyr	synonymous	Exon 10 of 10	ENSP00000559636.1
	SLC2A1	ENST00000958848.1		c.1293C>T	p.Tyr431Tyr	synonymous	Exon 10 of 10	ENSP00000628907.1

Frequencies

GnomAD3 genomes AF: 0.00247 AC: 376 AN: 152224 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00815

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.000723 AC: 180 AN: 249090 AF XY: 0.000512

Gnomad AFR exome AF: 0.00956

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000987

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000362 AC: 529 AN: 1461700 Hom.: 2 Cov.: 32 AF XY: 0.000327 AC XY: 238 AN XY: 727178

African (AFR) AF: 0.00983 AC: 329 AN: 33478

American (AMR) AF: 0.000313 AC: 14 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86254

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53294

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.000109 AC: 121 AN: 1111954

Other (OTH) AF: 0.000927 AC: 56 AN: 60394

GnomAD4 genome AF: 0.00248 AC: 378 AN: 152342 Hom.: 2 Cov.: 32 AF XY: 0.00254 AC XY: 189 AN XY: 74506

African (AFR) AF: 0.00818 AC: 340 AN: 41580

American (AMR) AF: 0.00144 AC: 22 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68028

Other (OTH) AF: 0.00378 AC: 8 AN: 2114

Alfa AF: 0.000907 Hom.: 0

Bravo AF: 0.00292

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	not provided (2)
-	-	1	Childhood onset GLUT1 deficiency syndrome 2 (1)
-	-	1	Dystonia 9 (1)
-	-	1	Encephalopathy due to GLUT1 deficiency (1)
-	-	1	Epilepsy, idiopathic generalized, susceptibility to, 12 (1)
-	-	1	GLUT1 deficiency syndrome 1, autosomal recessive (1)
-	-	1	Hereditary cryohydrocytosis with reduced stomatin (1)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.39
DANN	Benign	0.46
PhyloP100		-1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs75485205; hg19: chr1-43392895; COSMIC: COSV65287789; COSMIC: COSV65287789;