rs1885343

Positions:

• chr11-35355043-A-G

Variant summary

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

The NM_004171.4(SLC1A2):​c.18-37527T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 152,184 control chromosomes in the GnomAD database, including 9,762 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 0.36 (9762 hom., cov: 32)
• Consequence: SLC1A2 NM_004171.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC1A2	NM_004171.4	c.18-37527T>C		intron_variant		ENST00000278379.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC1A2	ENST00000278379.9	c.18-37527T>C		intron_variant		1	NM_004171.4	P4

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54136 AN: 152066 Hom.: 9762 Cov.: 32

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.357

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.356 AC: 54139 AN: 152184 Hom.: 9762 Cov.: 32 AF XY: 0.361 AC XY: 26838 AN XY: 74414

Gnomad4 AFR AF: 0.320

Gnomad4 AMR AF: 0.354

Gnomad4 ASJ AF: 0.380

Gnomad4 EAS AF: 0.501

Gnomad4 SAS AF: 0.531

Gnomad4 FIN AF: 0.339

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.353

Alfa AF: 0.355 Hom.: 3000

Bravo AF: 0.354

Asia WGS AF: 0.455 AC: 1580 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.6
DANN	Benign	0.69

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: rs1885343; hg19: chr11-35376590;