rs16927393

chr11-35353841-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.18-36325A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0707 in 152,262 control chromosomes in the GnomAD database, including 588 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 0.071 (588 hom., cov: 32)
• Consequence: SLC1A2 NM_004171.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55

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 (AFR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC1A2	NM_004171.4	c.18-36325A>G		intron_variant		ENST00000278379.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC1A2	ENST00000278379.9	c.18-36325A>G		intron_variant		1	NM_004171.4	P4

Frequencies

GnomAD3 genomes AF: 0.0707 AC: 10751 AN: 152142 Hom.: 585 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.0450

Gnomad ASJ AF: 0.0541

Gnomad EAS AF: 0.0973

Gnomad SAS AF: 0.0334

Gnomad FIN AF: 0.0336

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0346

Gnomad OTH AF: 0.0622

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

GnomAD4 genome AF: 0.0707 AC: 10770 AN: 152262 Hom.: 588 Cov.: 32 AF XY: 0.0700 AC XY: 5214 AN XY: 74460

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.0449

Gnomad4 ASJ AF: 0.0541

Gnomad4 EAS AF: 0.0973

Gnomad4 SAS AF: 0.0328

Gnomad4 FIN AF: 0.0336

Gnomad4 NFE AF: 0.0346

Gnomad4 OTH AF: 0.0625

Alfa AF: 0.0435 Hom.: 282

Bravo AF: 0.0759

Asia WGS AF: 0.0800 AC: 278 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	8.0
Dann	Benign	0.48

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: rs16927393; hg19: chr11-35375388;