Variant chr11-35286822-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004171.4(SLC1A2):c.1221A>G(p.Val407Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 1,612,998 control chromosomes in the GnomAD database, including 50,548 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5243 hom., cov: 32)

Exomes 𝑓: 0.25 ( 45305 hom. )

Consequence

SLC1A2
NM_004171.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.513

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 11-35286822-T-C is Benign according to our data. Variant chr11-35286822-T-C is described in ClinVar as [Benign]. Clinvar id is 1165045.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.513 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC1A2	NM_004171.4 linkuse as main transcript	c.1221A>G	p.Val407Val	synonymous_variant	8/11	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.1221A>G	p.Val407Val	synonymous_variant	8/11	1	NM_004171.4	ENSP00000278379.3		P43004-1

Frequencies

GnomAD3 genomes

AF:

0.258

AC:

39258

AN:

151928

Hom.:

5221

Cov.:

show subpopulations

Gnomad AFR

AF:

0.275

Gnomad AMI

AF:

0.200

Gnomad AMR

AF:

0.298

Gnomad ASJ

AF:

0.204

Gnomad EAS

AF:

0.209

Gnomad SAS

AF:

0.0996

Gnomad FIN

AF:

0.318

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.250

Gnomad OTH

AF:

0.236

GnomAD3 exomes

AF:

0.244

AC:

61384

AN:

251244

Hom.:

8024

AF XY:

0.235

AC XY:

31940

AN XY:

135768

show subpopulations

Gnomad AFR exome

AF:

0.282

Gnomad AMR exome

AF:

0.308

Gnomad ASJ exome

AF:

0.209

Gnomad EAS exome

AF:

0.202

Gnomad SAS exome

AF:

0.112

Gnomad FIN exome

AF:

0.323

Gnomad NFE exome

AF:

0.250

Gnomad OTH exome

AF:

0.254

GnomAD4 exome

AF:

0.245

AC:

358436

AN:

1460954

Hom.:

45305

Cov.:

AF XY:

0.241

AC XY:

174832

AN XY:

726820

show subpopulations

Gnomad4 AFR exome

AF:

0.283

Gnomad4 AMR exome

AF:

0.304

Gnomad4 ASJ exome

AF:

0.211

Gnomad4 EAS exome

AF:

0.268

Gnomad4 SAS exome

AF:

0.114

Gnomad4 FIN exome

AF:

0.319

Gnomad4 NFE exome

AF:

0.249

Gnomad4 OTH exome

AF:

0.234

GnomAD4 genome

AF:

0.259

AC:

39321

AN:

152044

Hom.:

5243

Cov.:

AF XY:

0.259

AC XY:

19220

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.274

Gnomad4 AMR

AF:

0.299

Gnomad4 ASJ

AF:

0.204

Gnomad4 EAS

AF:

0.210

Gnomad4 SAS

AF:

0.0989

Gnomad4 FIN

AF:

0.318

Gnomad4 NFE

AF:

0.250

Gnomad4 OTH

AF:

0.243

Alfa

AF:

0.246

Hom.:

4836

Bravo

AF:

0.260

Asia WGS

AF:

0.201

AC:

697

AN:

3478

EpiCase

AF:

0.246

EpiControl

AF:

0.248

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 01, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Developmental and epileptic encephalopathy, 41

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

4.7

DANN

Benign

0.63

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