Genetic Variant SLC1A2:c.*1341T>A (chr11-35259553-A-T) – 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.*1341T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 152,220 control chromosomes in the GnomAD database, including 9,285 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 0.33 ( 9282 hom., cov: 33)

Exomes 𝑓: 0.36 ( 3 hom. )

Consequence

SLC1A2
NM_004171.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.575

Publications

10 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:

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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=-0.82).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.518 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.*1341T>A	3_prime_UTR	Exon 11 of 11	NP_004162.2
SLC1A2	NM_001439342.1		c.*1341T>A	3_prime_UTR	Exon 11 of 11	NP_001426271.1
SLC1A2	NM_001195728.3		c.*1341T>A	3_prime_UTR	Exon 12 of 12	NP_001182657.1	P43004-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC1A2	ENST00000278379.9	TSL:1 MANE Select	c.*1341T>A	3_prime_UTR	Exon 11 of 11	ENSP00000278379.3	P43004-1
SLC1A2	ENST00000395750.6	TSL:1	c.*1341T>A	3_prime_UTR	Exon 11 of 11	ENSP00000379099.2	A0A2U3TZS7
SLC1A2	ENST00000644779.1		c.*1341T>A	3_prime_UTR	Exon 14 of 14	ENSP00000494258.1	A0A2R8YD46

Frequencies

GnomAD3 genomes

AF:

0.326

AC:

49515

AN:

152046

Hom.:

9287

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.518

Gnomad AMR

AF:

0.347

Gnomad ASJ

AF:

0.464

Gnomad EAS

AF:

0.474

Gnomad SAS

AF:

0.533

Gnomad FIN

AF:

0.342

Gnomad MID

AF:

0.421

Gnomad NFE

AF:

0.398

Gnomad OTH

AF:

0.361

GnomAD4 exome

AF:

0.357

AC:

AN:

Hom.:

Cov.:

AF XY:

0.367

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.352

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.325

AC:

49508

AN:

152164

Hom.:

9282

Cov.:

AF XY:

0.332

AC XY:

24696

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.134

AC:

5546

AN:

41542

American (AMR)

AF:

0.347

AC:

5299

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.464

AC:

1610

AN:

3472

East Asian (EAS)

AF:

0.472

AC:

2448

AN:

5184

South Asian (SAS)

AF:

0.535

AC:

2581

AN:

4826

European-Finnish (FIN)

AF:

0.342

AC:

3611

AN:

10558

Middle Eastern (MID)

AF:

0.415

AC:

122

AN:

294

European-Non Finnish (NFE)

AF:

0.398

AC:

27059

AN:

67972

Other (OTH)

AF:

0.359

AC:

760

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1606

3211

4817

6422

8028

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

512

1024

1536

2048

2560

<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:

0.358

Hom.:

1284

Bravo

AF:

0.314

Asia WGS

AF:

0.438

AC:

1521

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.90

(source)

DANN

Benign

0.46

PhyloP100

-0.57

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over