11-35306201-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_004171.4(SLC1A2):c.603G>A(p.Pro201=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 1,613,208 control chromosomes in the GnomAD database, including 48,375 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (3997 hom., cov: 32)
  • Exomes 𝑓: 0.24 (44378 hom.)
• Consequence: SLC1A2 NM_004171.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.26

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 11-35306201-C-T is Benign according to our data. Variant chr11-35306201-C-T is described in ClinVar as [Benign]. Clinvar id is 1165046.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.26 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC1A2	NM_004171.4	c.603G>A	p.Pro201=	synonymous_variant	5/11	ENST00000278379.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC1A2	ENST00000278379.9	c.603G>A	p.Pro201=	synonymous_variant	5/11	1	NM_004171.4	P4

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33297 AN: 151812 Hom.: 3980 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.0918

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.213

GnomAD3 exomes AF: 0.233 AC: 58560 AN: 251040 Hom.: 7414 AF XY: 0.227 AC XY: 30757 AN XY: 135656

Gnomad AFR exome AF: 0.138

Gnomad AMR exome AF: 0.296

Gnomad ASJ exome AF: 0.209

Gnomad EAS exome AF: 0.208

Gnomad SAS exome AF: 0.103

Gnomad FIN exome AF: 0.324

Gnomad NFE exome AF: 0.251

Gnomad OTH exome AF: 0.250

GnomAD4 exome AF: 0.242 AC: 353646 AN: 1461278 Hom.: 44378 Cov.: 33 AF XY: 0.237 AC XY: 172605 AN XY: 726972

Gnomad4 AFR exome AF: 0.138

Gnomad4 AMR exome AF: 0.292

Gnomad4 ASJ exome AF: 0.212

Gnomad4 EAS exome AF: 0.273

Gnomad4 SAS exome AF: 0.103

Gnomad4 FIN exome AF: 0.319

Gnomad4 NFE exome AF: 0.251

Gnomad4 OTH exome AF: 0.223

GnomAD4 genome AF: 0.219 AC: 33343 AN: 151930 Hom.: 3997 Cov.: 32 AF XY: 0.221 AC XY: 16406 AN XY: 74244

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.214

Gnomad4 SAS AF: 0.0910

Gnomad4 FIN AF: 0.320

Gnomad4 NFE AF: 0.251

Gnomad4 OTH AF: 0.221

Alfa AF: 0.240 Hom.: 10390

Bravo AF: 0.217

Asia WGS AF: 0.186 AC: 647 AN: 3476

EpiCase AF: 0.247

EpiControl AF: 0.250

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

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	-0.79
Cadd	Benign	3.7
Dann	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs752949; hg19: chr11-35327748; COSMIC: COSV53519625; COSMIC: COSV53519625;