rs11033052

Variant names:

• chr11-35288591-T-C
• rs11033052
• NM_004171.4:c.1092-1640A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004171.4(SLC1A2):​c.1092-1640A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 152,004 control chromosomes in the GnomAD database, including 27,779 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.60 (27779 hom., cov: 32)
• Consequence: SLC1A2 NM_004171.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 41

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A2	NM_004171.4	c.1092-1640A>G		intron_variant	Intron 7 of 10	ENST00000278379.9	NP_004162.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A2	ENST00000278379.9	c.1092-1640A>G		intron_variant	Intron 7 of 10	1	NM_004171.4	ENSP00000278379.3

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90690 AN: 151886 Hom.: 27756 Cov.: 32

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.732

Gnomad SAS AF: 0.643

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.611

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.597 AC: 90761 AN: 152004 Hom.: 27779 Cov.: 32 AF XY: 0.604 AC XY: 44914 AN XY: 74312

African (AFR) AF: 0.444 AC: 18411 AN: 41430

American (AMR) AF: 0.650 AC: 9936 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.674 AC: 2338 AN: 3468

East Asian (EAS) AF: 0.732 AC: 3790 AN: 5178

South Asian (SAS) AF: 0.644 AC: 3099 AN: 4812

European-Finnish (FIN) AF: 0.665 AC: 7022 AN: 10554

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.648 AC: 44018 AN: 67970

Other (OTH) AF: 0.616 AC: 1299 AN: 2110

Alfa AF: 0.620 Hom.: 5039

Bravo AF: 0.587

Asia WGS AF: 0.679 AC: 2357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.83
DANN	Benign	0.59
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11033052; hg19: chr11-35310138;