rs3794087

Positions:

• chr11-35308068-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.562-1826C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,166 control chromosomes in the GnomAD database, including 3,465 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 0.20 (3465 hom., cov: 32)
• Consequence: SLC1A2 NM_004171.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.438

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC1A2	NM_004171.4	c.562-1826C>A		intron_variant		ENST00000278379.9	NP_004162.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC1A2	ENST00000278379.9	c.562-1826C>A		intron_variant		1	NM_004171.4	ENSP00000278379	P4

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30115 AN: 152048 Hom.: 3445 Cov.: 32

Gnomad AFR AF: 0.0837

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.198 AC: 30155 AN: 152166 Hom.: 3465 Cov.: 32 AF XY: 0.200 AC XY: 14883 AN XY: 74386

Gnomad4 AFR AF: 0.0835

Gnomad4 AMR AF: 0.272

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.293

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.208

Alfa AF: 0.236 Hom.: 8809

Bravo AF: 0.195

Asia WGS AF: 0.189 AC: 656 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.60
DANN	Benign	0.43

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: rs3794087; hg19: chr11-35329615;