dbSNP rs2273686: SLC1A2:c.157+22C>T (chr11-35317355-G-A) – 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.157+22C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.093 in 1,606,928 control chromosomes in the GnomAD database, including 8,244 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 0.11 ( 1100 hom., cov: 32)

Exomes 𝑓: 0.091 ( 7144 hom. )

Consequence

SLC1A2
NM_004171.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.281

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A2	NM_004171.4 link	c.157+22C>T		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+22C>T		intron_variant	Intron 2 of 10	1	NM_004171.4	ENSP00000278379.3		P43004-1

Frequencies

GnomAD3 genomes

AF:

0.110

AC:

16749

AN:

152092

Hom.:

1098

Cov.:

show subpopulations

Gnomad AFR

AF:

0.148

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.155

Gnomad ASJ

AF:

0.158

Gnomad EAS

AF:

0.194

Gnomad SAS

AF:

0.145

Gnomad FIN

AF:

0.0639

Gnomad MID

AF:

0.150

Gnomad NFE

AF:

0.0735

Gnomad OTH

AF:

0.122

GnomAD2 exomes

AF:

0.117

AC:

28991

AN:

247906

AF XY:

0.115

show subpopulations

Gnomad AFR exome

AF:

0.151

Gnomad AMR exome

AF:

0.193

Gnomad ASJ exome

AF:

0.169

Gnomad EAS exome

AF:

0.194

Gnomad FIN exome

AF:

0.0633

Gnomad NFE exome

AF:

0.0726

Gnomad OTH exome

AF:

0.107

GnomAD4 exome

AF:

0.0912

AC:

132643

AN:

1454718

Hom.:

7144

Cov.:

AF XY:

0.0928

AC XY:

67002

AN XY:

722374

show subpopulations

African (AFR)

AF:

0.152

AC:

5082

AN:

33340

American (AMR)

AF:

0.193

AC:

8579

AN:

44516

Ashkenazi Jewish (ASJ)

AF:

0.165

AC:

4298

AN:

26042

East Asian (EAS)

AF:

0.171

AC:

6729

AN:

39458

South Asian (SAS)

AF:

0.149

AC:

12800

AN:

86006

European-Finnish (FIN)

AF:

0.0602

AC:

3206

AN:

53230

Middle Eastern (MID)

AF:

0.207

AC:

1183

AN:

5726

European-Non Finnish (NFE)

AF:

0.0762

AC:

84330

AN:

1106336

Other (OTH)

AF:

0.107

AC:

6436

AN:

60064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

5909

11819

17728

23638

29547

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.110

AC:

16757

AN:

152210

Hom.:

1100

Cov.:

AF XY:

0.111

AC XY:

8251

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.148

AC:

6143

AN:

41508

American (AMR)

AF:

0.155

AC:

2368

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.158

AC:

550

AN:

3472

East Asian (EAS)

AF:

0.194

AC:

1003

AN:

5176

South Asian (SAS)

AF:

0.145

AC:

700

AN:

4822

European-Finnish (FIN)

AF:

0.0639

AC:

678

AN:

10614

Middle Eastern (MID)

AF:

0.154

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0734

AC:

4995

AN:

68008

Other (OTH)

AF:

0.122

AC:

257

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

748

1497

2245

2994

3742

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0983

Hom.:

293

Bravo

AF:

0.121

Asia WGS

AF:

0.143

AC:

499

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.28

(source)

DANN

Benign

0.72

PhyloP100

-0.28

PromoterAI

-0.017

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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rs2273686

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