Variant rs56205617 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001195728.3(SLC1A2):c.-11+1G>A variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0295 in 1,516,772 control chromosomes in the GnomAD database, including 761 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in Lovd as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.033 ( 95 hom., cov: 32)

Exomes 𝑓: 0.029 ( 666 hom. )

Consequence

SLC1A2
NM_001195728.3 splice_donor, intron

Scores

Splicing: ADA: 0.00006553

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.27

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 11-35322560-C-T is Benign according to our data. Variant chr11-35322560-C-T is described in Lovd as [Likely_benign].

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC1A2	NM_004171.4 link	c.18-5044G>A		intron_variant		ENST00000278379.9	NP_004162.2	P43004-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC1A2	ENST00000278379.9 link	c.18-5044G>A		intron_variant		1	NM_004171.4	ENSP00000278379.3		P43004-1

Frequencies

GnomAD3 genomes

AF:

0.0333

AC:

5063

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0433

Gnomad AMI

AF:

0.0932

Gnomad AMR

AF:

0.0285

Gnomad ASJ

AF:

0.0499

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0147

Gnomad FIN

AF:

0.0260

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0313

Gnomad OTH

AF:

0.0377

GnomAD3 exomes

AF:

0.0263

AC:

3368

AN:

127894

Hom.:

AF XY:

0.0260

AC XY:

1818

AN XY:

70036

show subpopulations

Gnomad AFR exome

AF:

0.0460

Gnomad AMR exome

AF:

0.0203

Gnomad ASJ exome

AF:

0.0428

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0168

Gnomad FIN exome

AF:

0.0304

Gnomad NFE exome

AF:

0.0330

Gnomad OTH exome

AF:

0.0377

GnomAD4 exome

AF:

0.0290

AC:

39620

AN:

1364492

Hom.:

666

Cov.:

AF XY:

0.0290

AC XY:

19533

AN XY:

674592

show subpopulations

Gnomad4 AFR exome

AF:

0.0468

Gnomad4 AMR exome

AF:

0.0209

Gnomad4 ASJ exome

AF:

0.0458

Gnomad4 EAS exome

AF:

0.0000281

Gnomad4 SAS exome

AF:

0.0162

Gnomad4 FIN exome

AF:

0.0300

Gnomad4 NFE exome

AF:

0.0299

Gnomad4 OTH exome

AF:

0.0330

GnomAD4 genome

AF:

0.0333

AC:

5065

AN:

152280

Hom.:

Cov.:

AF XY:

0.0327

AC XY:

2434

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0432

Gnomad4 AMR

AF:

0.0285

Gnomad4 ASJ

AF:

0.0499

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0147

Gnomad4 FIN

AF:

0.0260

Gnomad4 NFE

AF:

0.0313

Gnomad4 OTH

AF:

0.0378

Alfa

AF:

0.0335

Hom.:

Bravo

AF:

0.0341

TwinsUK

AF:

0.0272

AC:

101

ALSPAC

AF:

0.0324

AC:

125

ExAC

AF:

0.0188

AC:

309

Asia WGS

AF:

0.00866

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.076

DANN

Benign

0.42

FATHMM_MKL

Benign

0.0020

GERP RS

-4.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000066

dbscSNV1_RF

Benign

0.020

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over