dbSNP rs77619780: SLC1A2:c.5+172G>A (chr11-35419764-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001439342.1(SLC1A2):c.5+172G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.013 in 280,718 control chromosomes in the GnomAD database, including 56 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 0.013 ( 30 hom., cov: 31)

Exomes 𝑓: 0.013 ( 26 hom. )

Consequence

SLC1A2
NM_001439342.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0740

Publications

2 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 links:

SLC1A2-AS2 (HGNC:40535): (SLC1A2 antisense RNA 2)

SLC1A2-AS2 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=-0.71).

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0129 (1967/152264) while in subpopulation AMR AF = 0.0389 (595/15300). AF 95% confidence interval is 0.0363. There are 30 homozygotes in GnomAd4. There are 990 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 30 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001439342.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC1A2	NM_001439342.1	c.5+172G>A	intron	N/A	NP_001426271.1
SLC1A2	NM_001195728.3	c.-130+172G>A	intron	N/A	NP_001182657.1	P43004-2
SLC1A2	NM_001252652.2	c.-167+144G>A	intron	N/A	NP_001239581.1	P43004-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC1A2	ENST00000395750.6	TSL:1	c.5+172G>A	intron	N/A	ENSP00000379099.2	A0A2U3TZS7
SLC1A2	ENST00000901505.1		c.-42+172G>A	intron	N/A	ENSP00000571564.1
SLC1A2	ENST00000395753.6	TSL:2	c.-11+144G>A	intron	N/A	ENSP00000379102.1	P43004-2

Frequencies

GnomAD3 genomes

AF:

0.0129

AC:

1962

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00306

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0387

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.0319

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.0278

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0107

Gnomad OTH

AF:

0.0167

GnomAD4 exome

AF:

0.0130

AC:

1676

AN:

128454

Hom.:

Cov.:

AF XY:

0.0120

AC XY:

851

AN XY:

70930

show subpopulations

African (AFR)

AF:

0.00340

AC:

AN:

2352

American (AMR)

AF:

0.0467

AC:

281

AN:

6018

Ashkenazi Jewish (ASJ)

AF:

0.00343

AC:

AN:

2626

East Asian (EAS)

AF:

0.0345

AC:

AN:

2814

South Asian (SAS)

AF:

0.00304

AC:

AN:

27322

European-Finnish (FIN)

AF:

0.0249

AC:

509

AN:

20456

Middle Eastern (MID)

AF:

0.00

AC:

AN:

354

European-Non Finnish (NFE)

AF:

0.0104

AC:

638

AN:

61206

Other (OTH)

AF:

0.00961

AC:

AN:

5306

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

158

237

316

395

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0129

AC:

1967

AN:

152264

Hom.:

Cov.:

AF XY:

0.0133

AC XY:

990

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.00306

AC:

127

AN:

41566

American (AMR)

AF:

0.0389

AC:

595

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00317

AC:

AN:

3468

East Asian (EAS)

AF:

0.0320

AC:

165

AN:

5156

South Asian (SAS)

AF:

0.00269

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0278

AC:

295

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0107

AC:

726

AN:

68020

Other (OTH)

AF:

0.0166

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

101

201

302

402

503

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.0101

Hom.:

Bravo

AF:

0.0141

Asia WGS

AF:

0.0170

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Benign

0.95

PhyloP100

0.074

PromoterAI

0.033

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over