rs41352148

Variant names:

• chr11-35287989-T-C
• rs41352148
• NM_004171.4:c.1092-1038A>G

Variant summary

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

The NM_004171.4(SLC1A2):​c.1092-1038A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,082 control chromosomes in the GnomAD database, including 5,230 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 0.26 (5230 hom., cov: 32)
• Consequence: SLC1A2 NM_004171.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.681

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=-0.73).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A2	NM_004171.4	c.1092-1038A>G		intron_variant	Intron 7 of 10	ENST00000278379.9	NP_004162.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A2	ENST00000278379.9	c.1092-1038A>G		intron_variant	Intron 7 of 10	1	NM_004171.4	ENSP00000278379.3

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39221 AN: 151964 Hom.: 5207 Cov.: 32

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.236

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

GnomAD4 genome AF: 0.258 AC: 39287 AN: 152082 Hom.: 5230 Cov.: 32 AF XY: 0.259 AC XY: 19226 AN XY: 74356

Gnomad4 AFR AF: 0.273

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.211

Gnomad4 SAS AF: 0.0995

Gnomad4 FIN AF: 0.319

Gnomad4 NFE AF: 0.250

Gnomad4 OTH AF: 0.244

Alfa AF: 0.257 Hom.: 833

Bravo AF: 0.259

Asia WGS AF: 0.202 AC: 699 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	11
DANN	Benign	0.88

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: rs41352148; hg19: chr11-35309536;