rs1042113

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.1221A>G(p.Val407Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 1,612,998 control chromosomes in the GnomAD database, including 50,548 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5243 hom., cov: 32)

Exomes 𝑓: 0.25 ( 45305 hom. )

Consequence

SLC1A2
NM_004171.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.513

Publications

27 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:

Genome browser will be placed here

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=-0.52).

BP6

Variant 11-35286822-T-C is Benign according to our data. Variant chr11-35286822-T-C is described in ClinVar as Benign. ClinVar VariationId is 1165045.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.513 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A2	NM_004171.4 link	c.1221A>G	p.Val407Val	synonymous_variant	Exon 8 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.1221A>G	p.Val407Val	synonymous_variant	Exon 8 of 11	1	NM_004171.4	ENSP00000278379.3		P43004-1

Frequencies

GnomAD3 genomes

AF:

0.258

AC:

39258

AN:

151928

Hom.:

5221

Cov.:

show subpopulations

Gnomad AFR

AF:

0.275

Gnomad AMI

AF:

0.200

Gnomad AMR

AF:

0.298

Gnomad ASJ

AF:

0.204

Gnomad EAS

AF:

0.209

Gnomad SAS

AF:

0.0996

Gnomad FIN

AF:

0.318

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.250

Gnomad OTH

AF:

0.236

GnomAD2 exomes

AF:

0.244

AC:

61384

AN:

251244

AF XY:

0.235

show subpopulations

Gnomad AFR exome

AF:

0.282

Gnomad AMR exome

AF:

0.308

Gnomad ASJ exome

AF:

0.209

Gnomad EAS exome

AF:

0.202

Gnomad FIN exome

AF:

0.323

Gnomad NFE exome

AF:

0.250

Gnomad OTH exome

AF:

0.254

GnomAD4 exome

AF:

0.245

AC:

358436

AN:

1460954

Hom.:

45305

Cov.:

AF XY:

0.241

AC XY:

174832

AN XY:

726820

show subpopulations

African (AFR)

AF:

0.283

AC:

9454

AN:

33448

American (AMR)

AF:

0.304

AC:

13597

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.211

AC:

5500

AN:

26122

East Asian (EAS)

AF:

0.268

AC:

10629

AN:

39686

South Asian (SAS)

AF:

0.114

AC:

9796

AN:

86224

European-Finnish (FIN)

AF:

0.319

AC:

17021

AN:

53420

Middle Eastern (MID)

AF:

0.200

AC:

1153

AN:

5752

European-Non Finnish (NFE)

AF:

0.249

AC:

277185

AN:

1111244

Other (OTH)

AF:

0.234

AC:

14101

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

13041

26083

39124

52166

65207

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9396

18792

28188

37584

46980

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.259

AC:

39321

AN:

152044

Hom.:

5243

Cov.:

AF XY:

0.259

AC XY:

19220

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.274

AC:

11381

AN:

41470

American (AMR)

AF:

0.299

AC:

4573

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.204

AC:

708

AN:

3468

East Asian (EAS)

AF:

0.210

AC:

1084

AN:

5168

South Asian (SAS)

AF:

0.0989

AC:

476

AN:

4814

European-Finnish (FIN)

AF:

0.318

AC:

3357

AN:

10560

Middle Eastern (MID)

AF:

0.272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.250

AC:

16967

AN:

67976

Other (OTH)

AF:

0.243

AC:

513

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1488

2976

4464

5952

7440

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

378

756

1134

1512

1890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.248

Hom.:

6207

Bravo

AF:

0.260

Asia WGS

AF:

0.201

AC:

697

AN:

3478

EpiCase

AF:

0.246

EpiControl

AF:

0.248

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 01, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

-0.52

CADD

Benign

4.7

(source)

DANN

Benign

0.63

PhyloP100

0.51

PromoterAI

0.044

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=84/16

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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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