rs1570216

chr11-35260787-T-C

Variant summary

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

The NM_004171.4(SLC1A2):c.*107A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 828,966 control chromosomes in the GnomAD database, including 7,401 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 0.12 (1122 hom., cov: 33)
  • Exomes 𝑓: 0.13 (6279 hom.)
• Consequence: SLC1A2 NM_004171.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.977

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC1A2	NM_004171.4	c.*107A>G		3_prime_UTR_variant	11/11	ENST00000278379.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC1A2	ENST00000278379.9	c.*107A>G		3_prime_UTR_variant	11/11	1	NM_004171.4	P4

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17601 AN: 152170 Hom.: 1106 Cov.: 33

Gnomad AFR AF: 0.0688

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.0681

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.127

GnomAD4 exome AF: 0.131 AC: 88632 AN: 676678 Hom.: 6279 Cov.: 9 AF XY: 0.127 AC XY: 45888 AN XY: 360122

Gnomad4 AFR exome AF: 0.0701

Gnomad4 AMR exome AF: 0.182

Gnomad4 ASJ exome AF: 0.131

Gnomad4 EAS exome AF: 0.211

Gnomad4 SAS exome AF: 0.0768

Gnomad4 FIN exome AF: 0.138

Gnomad4 NFE exome AF: 0.131

Gnomad4 OTH exome AF: 0.127

GnomAD4 genome AF: 0.116 AC: 17648 AN: 152288 Hom.: 1122 Cov.: 33 AF XY: 0.117 AC XY: 8711 AN XY: 74460

Gnomad4 AFR AF: 0.0690

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.153

Gnomad4 SAS AF: 0.0678

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.135

Alfa AF: 0.129 Hom.: 2929

Bravo AF: 0.119

Asia WGS AF: 0.150 AC: 522 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	7.2
Dann	Benign	0.42
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1570216; hg19: chr11-35282334;