rs7115246

Positions:

• chr11-35264931-A-G

Variant summary

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

The ENST00000278379.9(SLC1A2):​c.1653+596T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 151,434 control chromosomes in the GnomAD database, including 18,942 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 0.49 (18917 hom., cov: 29)
  • Exomes 𝑓: 0.45 (25 hom.)
• Consequence: SLC1A2 ENST00000278379.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC1A2	NM_004171.4	c.1653+596T>C		intron_variant		ENST00000278379.9	NP_004162.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC1A2	ENST00000278379.9	c.1653+596T>C		intron_variant		1	NM_004171.4	ENSP00000278379	P4

Frequencies

GnomAD3 genomes AF: 0.494 AC: 74695 AN: 151170 Hom.: 18901 Cov.: 29

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.521

GnomAD4 exome AF: 0.447 AC: 76 AN: 170 Hom.: 25 Cov.: 0 AF XY: 0.460 AC XY: 46 AN XY: 100

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.444

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.494 AC: 74752 AN: 151264 Hom.: 18917 Cov.: 29 AF XY: 0.500 AC XY: 36932 AN XY: 73852

Gnomad4 AFR AF: 0.381

Gnomad4 AMR AF: 0.548

Gnomad4 ASJ AF: 0.593

Gnomad4 EAS AF: 0.626

Gnomad4 SAS AF: 0.606

Gnomad4 FIN AF: 0.477

Gnomad4 NFE AF: 0.528

Gnomad4 OTH AF: 0.527

Alfa AF: 0.499 Hom.: 2388

Bravo AF: 0.492

Asia WGS AF: 0.601 AC: 2086 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.28
DANN	Benign	0.37

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: rs7115246; hg19: chr11-35286478;