Genetic Variant SLC1A2:c.157+31C>G (chr11-35317346-G-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004171.4(SLC1A2):c.157+31C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 1,602,160 control chromosomes in the GnomAD database, including 41,850 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3423 hom., cov: 32)

Exomes 𝑓: 0.23 ( 38427 hom. )

Consequence

SLC1A2
NM_004171.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0770

Publications

5 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 11-35317346-G-C is Benign according to our data. Variant chr11-35317346-G-C is described in ClinVar as [Benign]. Clinvar id is 1332978.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A2	NM_004171.4 link	c.157+31C>G		intron_variant	Intron 2 of 10	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.157+31C>G		intron_variant	Intron 2 of 10	1	NM_004171.4	ENSP00000278379.3		P43004-1

Frequencies

GnomAD3 genomes

AF:

0.195

AC:

29664

AN:

152070

Hom.:

3404

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0800

Gnomad AMI

AF:

0.207

Gnomad AMR

AF:

0.268

Gnomad ASJ

AF:

0.251

Gnomad EAS

AF:

0.207

Gnomad SAS

AF:

0.0933

Gnomad FIN

AF:

0.287

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.237

Gnomad OTH

AF:

0.195

GnomAD2 exomes

AF:

0.219

AC:

53505

AN:

244394

AF XY:

0.213

show subpopulations

Gnomad AFR exome

AF:

0.0747

Gnomad AMR exome

AF:

0.290

Gnomad ASJ exome

AF:

0.259

Gnomad EAS exome

AF:

0.202

Gnomad FIN exome

AF:

0.279

Gnomad NFE exome

AF:

0.237

Gnomad OTH exome

AF:

0.249

GnomAD4 exome

AF:

0.226

AC:

327107

AN:

1449972

Hom.:

38427

Cov.:

AF XY:

0.222

AC XY:

159654

AN XY:

719306

show subpopulations

African (AFR)

AF:

0.0762

AC:

2536

AN:

33278

American (AMR)

AF:

0.285

AC:

12630

AN:

44300

Ashkenazi Jewish (ASJ)

AF:

0.261

AC:

6765

AN:

25942

East Asian (EAS)

AF:

0.267

AC:

10497

AN:

39352

South Asian (SAS)

AF:

0.103

AC:

8823

AN:

85770

European-Finnish (FIN)

AF:

0.276

AC:

14609

AN:

53000

Middle Eastern (MID)

AF:

0.215

AC:

1226

AN:

5714

European-Non Finnish (NFE)

AF:

0.233

AC:

257376

AN:

1102836

Other (OTH)

AF:

0.212

AC:

12645

AN:

59780

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

11877

23753

35630

47506

59383

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8718

17436

26154

34872

43590

<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:

0.195

AC:

29703

AN:

152188

Hom.:

3423

Cov.:

AF XY:

0.197

AC XY:

14657

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.0798

AC:

3317

AN:

41554

American (AMR)

AF:

0.269

AC:

4112

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.251

AC:

871

AN:

3472

East Asian (EAS)

AF:

0.208

AC:

1073

AN:

5164

South Asian (SAS)

AF:

0.0927

AC:

447

AN:

4820

European-Finnish (FIN)

AF:

0.287

AC:

3041

AN:

10580

Middle Eastern (MID)

AF:

0.259

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.238

AC:

16148

AN:

67988

Other (OTH)

AF:

0.203

AC:

429

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1193

2387

3580

4774

5967

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

302

604

906

1208

1510

<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:

0.151

Hom.:

453

Bravo

AF:

0.191

Asia WGS

AF:

0.181

AC:

629

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

-0.83

CADD

Benign

1.1

(source)

DANN

Benign

0.37

PhyloP100

-0.077

PromoterAI

0.024

Neutral

(source)

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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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