11-35392417-C-G

Variant summary

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

The NM_004171.4(SLC1A2):c.17+26533G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 152,160 control chromosomes in the GnomAD database, including 10,901 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 0.37 (10893 hom., cov: 32)
  • Exomes 𝑓: 0.45 (8 hom.)
• Consequence: SLC1A2 NM_004171.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.132

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=-0.7).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC1A2	NM_004171.4	c.17+26533G>C		intron_variant		ENST00000278379.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC1A2	ENST00000278379.9	c.17+26533G>C		intron_variant		1	NM_004171.4	P4

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56380 AN: 151950 Hom.: 10900 Cov.: 32

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.364

GnomAD4 exome AF: 0.446 AC: 41 AN: 92 Hom.: 8 AF XY: 0.429 AC XY: 30 AN XY: 70

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 1.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.449

GnomAD4 genome AF: 0.371 AC: 56375 AN: 152068 Hom.: 10893 Cov.: 32 AF XY: 0.376 AC XY: 27918 AN XY: 74336

Gnomad4 AFR AF: 0.238

Gnomad4 AMR AF: 0.397

Gnomad4 ASJ AF: 0.440

Gnomad4 EAS AF: 0.421

Gnomad4 SAS AF: 0.456

Gnomad4 FIN AF: 0.433

Gnomad4 NFE AF: 0.423

Gnomad4 OTH AF: 0.359

Alfa AF: 0.277 Hom.: 708

Bravo AF: 0.361

Asia WGS AF: 0.400 AC: 1389 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	13
Dann	Benign	0.73

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: rs4534557; hg19: chr11-35413964;