11-35292626-C-T

Position:

• chr11-35292626-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.858-106G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0887 in 627,598 control chromosomes in the GnomAD database, including 3,117 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 0.10 (982 hom., cov: 32)
  • Exomes 𝑓: 0.084 (2135 hom.)
• Consequence: SLC1A2 NM_004171.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.180

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]

SLC1A2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC1A2	NM_004171.4	c.858-106G>A		intron_variant		ENST00000278379.9	NP_004162.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC1A2	ENST00000278379.9	c.858-106G>A		intron_variant		1	NM_004171.4	ENSP00000278379.3

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15740 AN: 151864 Hom.: 978 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.0551

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0604

Gnomad OTH AF: 0.121

GnomAD4 exome AF: 0.0839 AC: 39920 AN: 475616 Hom.: 2135 AF XY: 0.0862 AC XY: 21497 AN XY: 249268

Gnomad4 AFR exome AF: 0.151

Gnomad4 AMR exome AF: 0.172

Gnomad4 ASJ exome AF: 0.157

Gnomad4 EAS exome AF: 0.151

Gnomad4 SAS exome AF: 0.133

Gnomad4 FIN exome AF: 0.0461

Gnomad4 NFE exome AF: 0.0612

Gnomad4 OTH exome AF: 0.0986

GnomAD4 genome AF: 0.104 AC: 15747 AN: 151982 Hom.: 982 Cov.: 32 AF XY: 0.104 AC XY: 7710 AN XY: 74302

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.190

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.0551

Gnomad4 NFE AF: 0.0604

Gnomad4 OTH AF: 0.119

Alfa AF: 0.0755 Hom.: 1153

Bravo AF: 0.115

Asia WGS AF: 0.154 AC: 538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	2.6
DANN	Benign	0.68

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: rs2281634; hg19: chr11-35314173; COSMIC: COSV53525228;