rs1570214

chr11-35268272-A-Gchr11-35268272-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.1422-2514T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 152,066 control chromosomes in the GnomAD database, including 11,122 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 0.38 (11122 hom., cov: 32)
• Consequence: SLC1A2 NM_004171.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.359

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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC1A2	NM_004171.4	c.1422-2514T>C		intron_variant		ENST00000278379.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC1A2	ENST00000278379.9	c.1422-2514T>C		intron_variant		1	NM_004171.4	P4

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57570 AN: 151946 Hom.: 11119 Cov.: 32

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.397

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

GnomAD4 genome AF: 0.379 AC: 57599 AN: 152066 Hom.: 11122 Cov.: 32 AF XY: 0.383 AC XY: 28495 AN XY: 74328

Gnomad4 AFR AF: 0.325

Gnomad4 AMR AF: 0.367

Gnomad4 ASJ AF: 0.464

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.533

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.398

Gnomad4 OTH AF: 0.394

Alfa AF: 0.403 Hom.: 5890

Bravo AF: 0.374

Asia WGS AF: 0.441 AC: 1530 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.59
Dann	Benign	0.74

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: rs1570214; hg19: chr11-35289819;