rs10836370

Positions:

• chr11-35312485-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004171.4(SLC1A2):​c.311-37A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 1,606,604 control chromosomes in the GnomAD database, including 44,821 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (3777 hom., cov: 32)
  • Exomes 𝑓: 0.23 (41044 hom.)
• Consequence: SLC1A2 NM_004171.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.116

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-35312485-T-C is Benign according to our data. Variant chr11-35312485-T-C is described in ClinVar as [Benign]. Clinvar id is 1332977.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC1A2	NM_004171.4	c.311-37A>G		intron_variant		ENST00000278379.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC1A2	ENST00000278379.9	c.311-37A>G		intron_variant		1	NM_004171.4	P4

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31962 AN: 152112 Hom.: 3757 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.208

GnomAD3 exomes AF: 0.235 AC: 58197 AN: 248162 Hom.: 7171 AF XY: 0.229 AC XY: 30733 AN XY: 134454

Gnomad AFR exome AF: 0.106

Gnomad AMR exome AF: 0.292

Gnomad ASJ exome AF: 0.271

Gnomad EAS exome AF: 0.300

Gnomad SAS exome AF: 0.127

Gnomad FIN exome AF: 0.285

Gnomad NFE exome AF: 0.239

Gnomad OTH exome AF: 0.258

GnomAD4 exome AF: 0.232 AC: 337931 AN: 1454374 Hom.: 41044 Cov.: 31 AF XY: 0.229 AC XY: 165735 AN XY: 723010

Gnomad4 AFR exome AF: 0.109

Gnomad4 AMR exome AF: 0.288

Gnomad4 ASJ exome AF: 0.275

Gnomad4 EAS exome AF: 0.379

Gnomad4 SAS exome AF: 0.126

Gnomad4 FIN exome AF: 0.279

Gnomad4 NFE exome AF: 0.234

Gnomad4 OTH exome AF: 0.223

GnomAD4 genome AF: 0.210 AC: 32009 AN: 152230 Hom.: 3777 Cov.: 32 AF XY: 0.212 AC XY: 15799 AN XY: 74422

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.308

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.290

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.216

Alfa AF: 0.237 Hom.: 1714

Bravo AF: 0.207

Asia WGS AF: 0.256 AC: 890 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Developmental and epileptic encephalopathy, 41 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.7
DANN	Benign	0.45

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: rs10836370; hg19: chr11-35334032;