11-35306201-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004171.4(SLC1A2):c.603G>A(p.Pro201Pro) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.26

Publications

34 publications found

Variant links:

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 Gene-Disease associations (from GenCC):

developmental and epileptic encephalopathy, 41
Inheritance: AD, AR Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
undetermined early-onset epileptic encephalopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SLC1A2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SLC1A2	NM_004171.4 link	c.603G>A	p.Pro201Pro	synonymous_variant	Exon 5 of 11	ENST00000278379.9	NP_004162.2	P43004-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A2	ENST00000278379.9 link	c.603G>A	p.Pro201Pro	synonymous_variant	Exon 5 of 11	1	NM_004171.4	ENSP00000278379.3		P43004-1

Frequencies

GnomAD3 genomes

AF:

0.219

AC:

33297

AN:

151812

Hom.:

3980

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.233

AC:

58560

AN:

251040

AF XY:

0.227

show subpopulations

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 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.:

AF XY:

0.237

AC XY:

172605

AN XY:

726972

show subpopulations

African (AFR)

AF:

0.138

AC:

4629

AN:

33460

American (AMR)

AF:

0.292

AC:

13045

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.212

AC:

5533

AN:

26122

East Asian (EAS)

AF:

0.273

AC:

10828

AN:

39690

South Asian (SAS)

AF:

0.103

AC:

8892

AN:

86232

European-Finnish (FIN)

AF:

0.319

AC:

17046

AN:

53380

Middle Eastern (MID)

AF:

0.192

AC:

1105

AN:

5766

European-Non Finnish (NFE)

AF:

0.251

AC:

279088

AN:

1111548

Other (OTH)

AF:

0.223

AC:

13480

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

13147

26294

39442

52589

65736

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.219

AC:

33343

AN:

151930

Hom.:

3997

Cov.:

AF XY:

0.221

AC XY:

16406

AN XY:

74244

show subpopulations

African (AFR)

AF:

0.136

AC:

5643

AN:

41432

American (AMR)

AF:

0.282

AC:

4301

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.205

AC:

712

AN:

3468

East Asian (EAS)

AF:

0.214

AC:

1106

AN:

5166

South Asian (SAS)

AF:

0.0910

AC:

438

AN:

4812

European-Finnish (FIN)

AF:

0.320

AC:

3364

AN:

10526

Middle Eastern (MID)

AF:

0.259

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.251

AC:

17050

AN:

67982

Other (OTH)

AF:

0.221

AC:

465

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1281

2561

3842

5122

6403

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.238

Hom.:

20060

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:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Developmental and epileptic encephalopathy, 41

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

3.7

(source)

DANN

Benign

0.65

PhyloP100

-1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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11-35306201-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over