rs2273686

Positions:

• chr11-35317355-G-A
• chr11-35317355-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004171.4(SLC1A2):​c.157+22C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.093 in 1,606,928 control chromosomes in the GnomAD database, including 8,244 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 0.11 (1100 hom., cov: 32)
  • Exomes 𝑓: 0.091 (7144 hom.)
• Consequence: SLC1A2 NM_004171.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.281

Genes affected

SLC1A2 (HGNC:10940): (solute carrier family 1 member 2) This gene encodes a member of a family of solute transporter proteins. The membrane-bound protein is the principal transporter that clears the excitatory neurotransmitter glutamate from the extracellular space at synapses in the central nervous system. Glutamate clearance is necessary for proper synaptic activation and to prevent neuronal damage from excessive activation of glutamate receptors. Improper regulation of this gene is thought to be associated with several neurological disorders. Alternatively spliced transcript variants of this gene have been identified. [provided by RefSeq, Jun 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC1A2	NM_004171.4	c.157+22C>T		intron_variant		ENST00000278379.9	NP_004162.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC1A2	ENST00000278379.9	c.157+22C>T		intron_variant		1	NM_004171.4	ENSP00000278379.3

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16749 AN: 152092 Hom.: 1098 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.0639

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.0735

Gnomad OTH AF: 0.122

GnomAD3 exomes AF: 0.117 AC: 28991 AN: 247906 Hom.: 2014 AF XY: 0.115 AC XY: 15456 AN XY: 134078

Gnomad AFR exome AF: 0.151

Gnomad AMR exome AF: 0.193

Gnomad ASJ exome AF: 0.169

Gnomad EAS exome AF: 0.194

Gnomad SAS exome AF: 0.152

Gnomad FIN exome AF: 0.0633

Gnomad NFE exome AF: 0.0726

Gnomad OTH exome AF: 0.107

GnomAD4 exome AF: 0.0912 AC: 132643 AN: 1454718 Hom.: 7144 Cov.: 32 AF XY: 0.0928 AC XY: 67002 AN XY: 722374

Gnomad4 AFR exome AF: 0.152

Gnomad4 AMR exome AF: 0.193

Gnomad4 ASJ exome AF: 0.165

Gnomad4 EAS exome AF: 0.171

Gnomad4 SAS exome AF: 0.149

Gnomad4 FIN exome AF: 0.0602

Gnomad4 NFE exome AF: 0.0762

Gnomad4 OTH exome AF: 0.107

GnomAD4 genome AF: 0.110 AC: 16757 AN: 152210 Hom.: 1100 Cov.: 32 AF XY: 0.111 AC XY: 8251 AN XY: 74430

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.0639

Gnomad4 NFE AF: 0.0734

Gnomad4 OTH AF: 0.122

Alfa AF: 0.104 Hom.: 184

Bravo AF: 0.121

Asia WGS AF: 0.143 AC: 499 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.28
DANN	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs2273686; hg19: chr11-35338902; COSMIC: COSV53525236; COSMIC: COSV53525236;