rs77619780

Positions:

• chr11-35419764-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000395750.6(SLC1A2):​c.5+172G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.013 in 280,718 control chromosomes in the GnomAD database, including 56 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 0.013 (30 hom., cov: 31)
  • Exomes 𝑓: 0.013 (26 hom.)
• Consequence: SLC1A2 ENST00000395750.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740

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]

SLC1A2-AS2 (HGNC:40535): (SLC1A2 antisense RNA 2)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0129 (1967/152264) while in subpopulation AMR AF= 0.0389 (595/15300). AF 95% confidence interval is 0.0363. There are 30 homozygotes in gnomad4. There are 990 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1967 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC1A2	NM_001195728.3	c.-130+172G>A		intron_variant
SLC1A2	NM_001252652.2	c.-167+144G>A		intron_variant
SLC1A2	XM_011520285.2	c.5+172G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC1A2-AS2	ENST00000534165.1	n.51+657C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0129 AC: 1962 AN: 152146 Hom.: 29 Cov.: 31

Gnomad AFR AF: 0.00306

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0387

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.0319

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.0278

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0107

Gnomad OTH AF: 0.0167

GnomAD4 exome AF: 0.0130 AC: 1676 AN: 128454 Hom.: 26 Cov.: 0 AF XY: 0.0120 AC XY: 851 AN XY: 70930

Gnomad4 AFR exome AF: 0.00340

Gnomad4 AMR exome AF: 0.0467

Gnomad4 ASJ exome AF: 0.00343

Gnomad4 EAS exome AF: 0.0345

Gnomad4 SAS exome AF: 0.00304

Gnomad4 FIN exome AF: 0.0249

Gnomad4 NFE exome AF: 0.0104

Gnomad4 OTH exome AF: 0.00961

GnomAD4 genome AF: 0.0129 AC: 1967 AN: 152264 Hom.: 30 Cov.: 31 AF XY: 0.0133 AC XY: 990 AN XY: 74444

Gnomad4 AFR AF: 0.00306

Gnomad4 AMR AF: 0.0389

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.0320

Gnomad4 SAS AF: 0.00269

Gnomad4 FIN AF: 0.0278

Gnomad4 NFE AF: 0.0107

Gnomad4 OTH AF: 0.0166

Alfa AF: 0.0101 Hom.: 0

Bravo AF: 0.0141

Asia WGS AF: 0.0170 AC: 60 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	15
DANN	Benign	0.95

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs77619780; hg19: chr11-35441311;