Genetic Variant SLC1A2:c.17+26533G>C (chr11-35392417-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004171.4(SLC1A2):c.17+26533G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 152,160 control chromosomes in the GnomAD database, including 10,901 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.37 ( 10893 hom., cov: 32)

Exomes 𝑓: 0.45 ( 8 hom. )

Consequence

SLC1A2
NM_004171.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.132

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A2	NM_004171.4 link	c.17+26533G>C		intron_variant	Intron 1 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.17+26533G>C		intron_variant	Intron 1 of 10	1	NM_004171.4	ENSP00000278379.3		P43004-1

Frequencies

GnomAD3 genomes

AF:

0.371

AC:

56380

AN:

151950

Hom.:

10900

Cov.:

show subpopulations

Gnomad AFR

AF:

0.238

Gnomad AMI

AF:

0.368

Gnomad AMR

AF:

0.398

Gnomad ASJ

AF:

0.440

Gnomad EAS

AF:

0.422

Gnomad SAS

AF:

0.455

Gnomad FIN

AF:

0.433

Gnomad MID

AF:

0.433

Gnomad NFE

AF:

0.423

Gnomad OTH

AF:

0.364

GnomAD4 exome

AF:

0.446

AC:

AN:

Hom.:

AF XY:

0.429

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.333

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.449

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.371

AC:

56375

AN:

152068

Hom.:

10893

Cov.:

AF XY:

0.376

AC XY:

27918

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.238

AC:

9867

AN:

41486

American (AMR)

AF:

0.397

AC:

6069

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.440

AC:

1525

AN:

3468

East Asian (EAS)

AF:

0.421

AC:

2171

AN:

5154

South Asian (SAS)

AF:

0.456

AC:

2198

AN:

4820

European-Finnish (FIN)

AF:

0.433

AC:

4571

AN:

10548

Middle Eastern (MID)

AF:

0.438

AC:

128

AN:

292

European-Non Finnish (NFE)

AF:

0.423

AC:

28753

AN:

67996

Other (OTH)

AF:

0.359

AC:

758

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1816

3632

5448

7264

9080

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

562

1124

1686

2248

2810

<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:

0.277

Hom.:

708

Bravo

AF:

0.361

Asia WGS

AF:

0.400

AC:

1389

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.73

PhyloP100

-0.13

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

Computational scores

Splicing

Publications

Other links and lift over