rs2421765

Positions:

• chr11-35299458-C-A
• chr11-35299458-C-G
• chr11-35299458-C-T

Variant summary

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

The NM_004171.4(SLC1A2):​c.857+2061G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 151,482 control chromosomes in the GnomAD database, including 25,738 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 0.56 (25737 hom., cov: 29)
  • Exomes 𝑓: 0.75 (1 hom.)
• Consequence: SLC1A2 NM_004171.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC1A2	NM_004171.4	c.857+2061G>T		intron_variant		ENST00000278379.9	NP_004162.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC1A2	ENST00000278379.9	c.857+2061G>T		intron_variant		1	NM_004171.4	ENSP00000278379	P4

Frequencies

GnomAD3 genomes AF: 0.560 AC: 84816 AN: 151360 Hom.: 25724 Cov.: 29

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.716

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.738

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.669

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.653

Gnomad OTH AF: 0.593

GnomAD4 exome AF: 0.750 AC: 3 AN: 4 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

Gnomad4 NFE exome AF: 0.750

GnomAD4 genome AF: 0.560 AC: 84861 AN: 151478 Hom.: 25737 Cov.: 29 AF XY: 0.569 AC XY: 42135 AN XY: 74018

Gnomad4 AFR AF: 0.300

Gnomad4 AMR AF: 0.640

Gnomad4 ASJ AF: 0.690

Gnomad4 EAS AF: 0.738

Gnomad4 SAS AF: 0.654

Gnomad4 FIN AF: 0.669

Gnomad4 NFE AF: 0.653

Gnomad4 OTH AF: 0.598

Alfa AF: 0.602 Hom.: 4902

Bravo AF: 0.546

Asia WGS AF: 0.671 AC: 2327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.91
DANN	Benign	0.61

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: rs2421765; hg19: chr11-35321005;