dbSNP rs7115246: SLC1A2:c.1653+596T>C (chr11-35264931-A-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.1653+596T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 151,434 control chromosomes in the GnomAD database, including 18,942 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 0.49 ( 18917 hom., cov: 29)

Exomes 𝑓: 0.45 ( 25 hom. )

Consequence

SLC1A2
NM_004171.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.77

Publications

3 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-AS1 (HGNC:40534): (SLC1A2 antisense RNA 1)

SLC1A2-AS1 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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004171.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC1A2	NM_004171.4	MANE Select	c.1653+596T>C	intron	N/A	NP_004162.2
SLC1A2	NM_001439342.1		c.1641+596T>C	intron	N/A	NP_001426271.1
SLC1A2	NM_001195728.3		c.1626+596T>C	intron	N/A	NP_001182657.1	P43004-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC1A2	ENST00000278379.9	TSL:1 MANE Select	c.1653+596T>C	intron	N/A	ENSP00000278379.3	P43004-1
SLC1A2	ENST00000395750.6	TSL:1	c.1641+596T>C	intron	N/A	ENSP00000379099.2	A0A2U3TZS7
SLC1A2	ENST00000643454.1		c.*557T>C	3_prime_UTR	Exon 10 of 10	ENSP00000495126.1	A0A2R8Y5Y1

Frequencies

GnomAD3 genomes

AF:

0.494

AC:

74695

AN:

151170

Hom.:

18901

Cov.:

show subpopulations

Gnomad AFR

AF:

0.381

Gnomad AMI

AF:

0.578

Gnomad AMR

AF:

0.548

Gnomad ASJ

AF:

0.593

Gnomad EAS

AF:

0.628

Gnomad SAS

AF:

0.604

Gnomad FIN

AF:

0.477

Gnomad MID

AF:

0.564

Gnomad NFE

AF:

0.528

Gnomad OTH

AF:

0.521

GnomAD4 exome

AF:

0.447

AC:

AN:

170

Hom.:

Cov.:

AF XY:

0.460

AC XY:

AN XY:

100

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.444

AC:

AN:

144

Other (OTH)

AF:

0.750

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.552

Heterozygous variant carriers

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:

0.494

AC:

74752

AN:

151264

Hom.:

18917

Cov.:

AF XY:

0.500

AC XY:

36932

AN XY:

73852

show subpopulations

African (AFR)

AF:

0.381

AC:

15645

AN:

41068

American (AMR)

AF:

0.548

AC:

8349

AN:

15226

Ashkenazi Jewish (ASJ)

AF:

0.593

AC:

2055

AN:

3466

East Asian (EAS)

AF:

0.626

AC:

3223

AN:

5146

South Asian (SAS)

AF:

0.606

AC:

2898

AN:

4782

European-Finnish (FIN)

AF:

0.477

AC:

4956

AN:

10382

Middle Eastern (MID)

AF:

0.562

AC:

163

AN:

290

European-Non Finnish (NFE)

AF:

0.528

AC:

35827

AN:

67888

Other (OTH)

AF:

0.527

AC:

1110

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1889

3779

5668

7558

9447

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

676

1352

2028

2704

3380

<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:

0.499

Hom.:

2388

Bravo

AF:

0.492

Asia WGS

AF:

0.601

AC:

2086

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.28

(source)

DANN

Benign

0.37

PhyloP100

-1.8

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over