Variant 11-35301653-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004171.4(SLC1A2):c.731-8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 1,611,004 control chromosomes in the GnomAD database, including 332,185 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 ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.56 ( 25817 hom., cov: 32)

Exomes 𝑓: 0.64 ( 306368 hom. )

Consequence

SLC1A2
NM_004171.4 splice_region, intron

Scores

Splicing: ADA: 0.0001068

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.401

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 11-35301653-A-G is Benign according to our data. Variant chr11-35301653-A-G is described in ClinVar as [Benign]. Clinvar id is 1169957.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.718 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.731-8T>C		splice_region_variant, 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 linkuse as main transcript	c.731-8T>C		splice_region_variant, intron_variant		1	NM_004171.4	ENSP00000278379.3		P43004-1

Frequencies

GnomAD3 genomes

AF:

0.560

AC:

85113

AN:

152002

Hom.:

25804

Cov.:

show subpopulations

Gnomad AFR

AF:

0.300

Gnomad AMI

AF:

0.720

Gnomad AMR

AF:

0.639

Gnomad ASJ

AF:

0.690

Gnomad EAS

AF:

0.737

Gnomad SAS

AF:

0.652

Gnomad FIN

AF:

0.667

Gnomad MID

AF:

0.678

Gnomad NFE

AF:

0.653

Gnomad OTH

AF:

0.593

GnomAD3 exomes

AF:

0.640

AC:

159643

AN:

249370

Hom.:

52223

AF XY:

0.646

AC XY:

87182

AN XY:

134862

show subpopulations

Gnomad AFR exome

AF:

0.293

Gnomad AMR exome

AF:

0.642

Gnomad ASJ exome

AF:

0.679

Gnomad EAS exome

AF:

0.731

Gnomad SAS exome

AF:

0.651

Gnomad FIN exome

AF:

0.676

Gnomad NFE exome

AF:

0.660

Gnomad OTH exome

AF:

0.663

GnomAD4 exome

AF:

0.645

AC:

940839

AN:

1458884

Hom.:

306368

Cov.:

AF XY:

0.646

AC XY:

468952

AN XY:

725948

show subpopulations

Gnomad4 AFR exome

AF:

0.298

Gnomad4 AMR exome

AF:

0.639

Gnomad4 ASJ exome

AF:

0.681

Gnomad4 EAS exome

AF:

0.780

Gnomad4 SAS exome

AF:

0.651

Gnomad4 FIN exome

AF:

0.678

Gnomad4 NFE exome

AF:

0.649

Gnomad4 OTH exome

AF:

0.630

GnomAD4 genome

AF:

0.560

AC:

85158

AN:

152120

Hom.:

25817

Cov.:

AF XY:

0.569

AC XY:

42304

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.300

Gnomad4 AMR

AF:

0.639

Gnomad4 ASJ

AF:

0.690

Gnomad4 EAS

AF:

0.737

Gnomad4 SAS

AF:

0.653

Gnomad4 FIN

AF:

0.667

Gnomad4 NFE

AF:

0.653

Gnomad4 OTH

AF:

0.597

Alfa

AF:

0.623

Hom.:

23014

Bravo

AF:

0.546

Asia WGS

AF:

0.671

AC:

2328

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

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

-0.66

CADD

Benign

8.6

DANN

Benign

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00011

dbscSNV1_RF

Benign

0.044

SpliceAI score (max)

0.020

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