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GeneBe

11-35260921-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_004171.4(SLC1A2):c.1698G>A(p.Glu566=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000469 in 1,613,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00026 ( 0 hom. )

Consequence

SLC1A2
NM_004171.4 synonymous

Scores

6

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.161
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (MetaRNN=0.006164938).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-35260921-C-T is Benign according to our data. Variant chr11-35260921-C-T is described in ClinVar as [Benign]. Clinvar id is 771955.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.161 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 375 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC1A2NM_004171.4 linkuse as main transcriptc.1698G>A p.Glu566= synonymous_variant 11/11 ENST00000278379.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC1A2ENST00000278379.9 linkuse as main transcriptc.1698G>A p.Glu566= synonymous_variant 11/111 NM_004171.4 P4P43004-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00247
AC:
375
AN:
152120
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00836
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000982
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00431
GnomAD3 exomes
AF:
0.000700
AC:
176
AN:
251436
Hom.:
0
AF XY:
0.000500
AC XY:
68
AN XY:
135892
show subpopulations
Gnomad AFR exome
AF:
0.00966
Gnomad AMR exome
AF:
0.000318
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000615
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000261
AC:
382
AN:
1461468
Hom.:
0
Cov.:
29
AF XY:
0.000226
AC XY:
164
AN XY:
727080
show subpopulations
Gnomad4 AFR exome
AF:
0.00828
Gnomad4 AMR exome
AF:
0.000358
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000504
Gnomad4 OTH exome
AF:
0.000447
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00246
AC:
375
AN:
152238
Hom.:
0
Cov.:
33
AF XY:
0.00214
AC XY:
159
AN XY:
74436
show subpopulations
Gnomad4 AFR
AF:
0.00833
Gnomad4 AMR
AF:
0.000980
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00427
Alfa
AF:
0.00118
Hom.:
0
Bravo
AF:
0.00290
ESP6500AA
AF:
0.00795
AC:
35
ESP6500EA
AF:
0.000116
AC:
1
ExAC
?
    Exome Aggregation Consortium database
AF:
0.000914
AC:
111
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000119

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 28, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.47
Cadd
Benign
5.0
Dann
Benign
0.79
FATHMM_MKL
Benign
0.71
D
LIST_S2
Benign
0.15
T
MetaRNN
Benign
0.0062
T
MutationTaster
Benign
1.0
D;D;D
GERP RS
-0.42

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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.

Other links and lift over

dbSNP: rs114945303; hg19: chr11-35282468; API