rs4756224

chr11-35369861-A-Gchr11-35369861-A-T

Variant summary

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

The NM_004171.4(SLC1A2):c.17+49089T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,064 control chromosomes in the GnomAD database, including 6,199 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 0.28 (6199 hom., cov: 32)
• Consequence: SLC1A2 NM_004171.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.84

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC1A2	NM_004171.4	c.17+49089T>C		intron_variant		ENST00000278379.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC1A2	ENST00000278379.9	c.17+49089T>C		intron_variant		1	NM_004171.4	P4

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42899 AN: 151946 Hom.: 6190 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.282 AC: 42931 AN: 152064 Hom.: 6199 Cov.: 32 AF XY: 0.280 AC XY: 20835 AN XY: 74324

Gnomad4 AFR AF: 0.333

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.281

Gnomad4 EAS AF: 0.221

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.265

Alfa AF: 0.132 Hom.: 202

Bravo AF: 0.281

Asia WGS AF: 0.261 AC: 905 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.043
Dann	Benign	0.63

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: rs4756224; hg19: chr11-35391408;