Variant rs16927239 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_004171.4(SLC1A2):c.1368C>T(p.Ala456Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00146 in 1,613,376 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00088 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 4 hom. )

Consequence

SLC1A2
NM_004171.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.45

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 (HGNC:):

SLC1A2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 11-35280920-G-A is Benign according to our data. Variant chr11-35280920-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 767309.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.45 with no splicing effect.

BS2

High AC in GnomAd4 at 134 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC1A2	NM_004171.4 linkuse as main transcript	c.1368C>T	p.Ala456Ala	synonymous_variant	9/11	ENST00000278379.9	NP_004162.2	P43004-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC1A2	ENST00000278379.9 linkuse as main transcript	c.1368C>T	p.Ala456Ala	synonymous_variant	9/11	1	NM_004171.4	ENSP00000278379.3		P43004-1

Frequencies

GnomAD3 genomes

AF:

0.000880

AC:

134

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00146

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00147

AC:

367

AN:

250306

Hom.:

AF XY:

0.00163

AC XY:

220

AN XY:

135266

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000204

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000547

Gnomad SAS exome

AF:

0.00496

Gnomad FIN exome

AF:

0.000462

Gnomad NFE exome

AF:

0.00166

Gnomad OTH exome

AF:

0.00164

GnomAD4 exome

AF:

0.00152

AC:

2222

AN:

1461052

Hom.:

Cov.:

AF XY:

0.00164

AC XY:

1195

AN XY:

726834

show subpopulations

Gnomad4 AFR exome

AF:

0.0000898

Gnomad4 AMR exome

AF:

0.000336

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.00452

Gnomad4 FIN exome

AF:

0.000786

Gnomad4 NFE exome

AF:

0.00149

Gnomad4 OTH exome

AF:

0.00154

GnomAD4 genome

AF:

0.000880

AC:

134

AN:

152324

Hom.:

Cov.:

AF XY:

0.000886

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00146

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00124

Hom.:

Bravo

AF:

0.000797

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00185

EpiControl

AF:

0.00166

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 24, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	SLC1A2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.23

DANN

Benign

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over