rs11033118

Positions:

• chr11-35419707-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001195728.3(SLC1A2):​c.-130+229C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00731 in 173,038 control chromosomes in the GnomAD database, including 6 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 0.0075 (6 hom., cov: 31)
  • Exomes 𝑓: 0.0057 (0 hom.)
• Consequence: SLC1A2 NM_001195728.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.637

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]

ENSG00000255542 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BS2: High AC in GnomAd4 at 1147 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC1A2	NM_001195728.3	c.-130+229C>T		intron_variant			NP_001182657.1
SLC1A2	NM_001252652.2	c.-167+201C>T		intron_variant			NP_001239581.1
SLC1A2	XM_011520285.2	c.5+229C>T		intron_variant			XP_011518587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC1A2	ENST00000395750.6	c.5+229C>T		intron_variant		1		ENSP00000379099.2
SLC1A2	ENST00000395753.6	c.-11+201C>T		intron_variant		2		ENSP00000379102.1
SLC1A2	ENST00000643000.1	c.-11+213C>T		intron_variant				ENSP00000495164.1

Frequencies

GnomAD3 genomes AF: 0.00755 AC: 1148 AN: 152078 Hom.: 6 Cov.: 31

Gnomad AFR AF: 0.00159

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00943

Gnomad ASJ AF: 0.00981

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00320

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0121

Gnomad OTH AF: 0.0129

GnomAD4 exome AF: 0.00566 AC: 118 AN: 20844 Hom.: 0 Cov.: 0 AF XY: 0.00596 AC XY: 69 AN XY: 11578

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00694

Gnomad4 ASJ exome AF: 0.0240

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00408

Gnomad4 FIN exome AF: 0.00149

Gnomad4 NFE exome AF: 0.0103

Gnomad4 OTH exome AF: 0.0117

GnomAD4 genome AF: 0.00754 AC: 1147 AN: 152194 Hom.: 6 Cov.: 31 AF XY: 0.00708 AC XY: 527 AN XY: 74416

Gnomad4 AFR AF: 0.00159

Gnomad4 AMR AF: 0.00941

Gnomad4 ASJ AF: 0.00981

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00270

Gnomad4 FIN AF: 0.00320

Gnomad4 NFE AF: 0.0121

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.00985 Hom.: 1

Bravo AF: 0.00846

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	16
DANN	Benign	0.94

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11033118; hg19: chr11-35441254;