rs10488815

Variant names:

• chr11-35265221-G-A
• rs10488815
• NM_004171.4:c.1653+306C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004171.4(SLC1A2):​c.1653+306C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0158 in 445,652 control chromosomes in the GnomAD database, including 186 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 0.017 (86 hom., cov: 31)
  • Exomes 𝑓: 0.015 (100 hom.)
• Consequence: SLC1A2 NM_004171.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.266
• Publications: 2 publications found

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-AS1 (HGNC:40534): (SLC1A2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A2	NM_004171.4	c.1653+306C>T		intron_variant	Intron 10 of 10	ENST00000278379.9	NP_004162.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A2	ENST00000278379.9	c.1653+306C>T		intron_variant	Intron 10 of 10	1	NM_004171.4	ENSP00000278379.3

Frequencies

GnomAD3 genomes AF: 0.0165 AC: 2516 AN: 152138 Hom.: 81 Cov.: 31

Gnomad AFR AF: 0.00256

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0865

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.0262

Gnomad SAS AF: 0.00415

Gnomad FIN AF: 0.00897

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0108

Gnomad OTH AF: 0.0163

GnomAD4 exome AF: 0.0153 AC: 4497 AN: 293396 Hom.: 100 Cov.: 0 AF XY: 0.0147 AC XY: 2237 AN XY: 151896

African (AFR) AF: 0.00222 AC: 18 AN: 8112

American (AMR) AF: 0.0953 AC: 960 AN: 10078

Ashkenazi Jewish (ASJ) AF: 0.0128 AC: 131 AN: 10270

East Asian (EAS) AF: 0.0376 AC: 875 AN: 23246

South Asian (SAS) AF: 0.00535 AC: 84 AN: 15712

European-Finnish (FIN) AF: 0.00978 AC: 191 AN: 19538

Middle Eastern (MID) AF: 0.00284 AC: 4 AN: 1406

European-Non Finnish (NFE) AF: 0.0107 AC: 1992 AN: 186986

Other (OTH) AF: 0.0134 AC: 242 AN: 18048

GnomAD4 genome AF: 0.0166 AC: 2532 AN: 152256 Hom.: 86 Cov.: 31 AF XY: 0.0184 AC XY: 1372 AN XY: 74436

African (AFR) AF: 0.00255 AC: 106 AN: 41560

American (AMR) AF: 0.0875 AC: 1338 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 41 AN: 3472

East Asian (EAS) AF: 0.0264 AC: 137 AN: 5184

South Asian (SAS) AF: 0.00415 AC: 20 AN: 4820

European-Finnish (FIN) AF: 0.00897 AC: 95 AN: 10592

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0108 AC: 733 AN: 68012

Other (OTH) AF: 0.0156 AC: 33 AN: 2112

Alfa AF: 0.0103 Hom.: 4

Bravo AF: 0.0224

Asia WGS AF: 0.0150 AC: 52 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	14
DANN	Benign	0.77
PhyloP100		0.27
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs10488815; hg19: chr11-35286768;