rs1923298

Variant names:

• chr11-35362885-T-C
• rs1923298
• NM_004171.4:c.18-45369A>G

Variant summary

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

The NM_004171.4(SLC1A2):​c.18-45369A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,120 control chromosomes in the GnomAD database, including 4,324 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 0.22 (4324 hom., cov: 32)
• Consequence: SLC1A2 NM_004171.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.293
• Publications: 5 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 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 41

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A2	NM_004171.4	c.18-45369A>G		intron_variant	Intron 1 of 10	ENST00000278379.9	NP_004162.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A2	ENST00000278379.9	c.18-45369A>G		intron_variant	Intron 1 of 10	1	NM_004171.4	ENSP00000278379.3

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33532 AN: 152002 Hom.: 4316 Cov.: 32

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.179

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.203

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.221 AC: 33578 AN: 152120 Hom.: 4324 Cov.: 32 AF XY: 0.219 AC XY: 16297 AN XY: 74374

African (AFR) AF: 0.356 AC: 14760 AN: 41474

American (AMR) AF: 0.175 AC: 2683 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 585 AN: 3464

East Asian (EAS) AF: 0.185 AC: 960 AN: 5184

South Asian (SAS) AF: 0.230 AC: 1109 AN: 4824

European-Finnish (FIN) AF: 0.181 AC: 1920 AN: 10586

Middle Eastern (MID) AF: 0.176 AC: 51 AN: 290

European-Non Finnish (NFE) AF: 0.159 AC: 10795 AN: 67982

Other (OTH) AF: 0.205 AC: 434 AN: 2114

Alfa AF: 0.180 Hom.: 11557

Bravo AF: 0.227

Asia WGS AF: 0.222 AC: 772 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.80
DANN	Benign	0.80
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

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: rs1923298; hg19: chr11-35384432;