11-35308068-G-T

Variant names:

• chr11-35308068-G-T
• rs3794087
• NM_004171.4:c.562-1826C>A

Variant summary

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

The NM_004171.4(SLC1A2):​c.562-1826C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,166 control chromosomes in the GnomAD database, including 3,465 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 0.20 (3465 hom., cov: 32)
• Consequence: SLC1A2 NM_004171.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.438
• Publications: 41 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004171.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A2	NM_004171.4	MANE Select	c.562-1826C>A		intron	N/A	NP_004162.2
	SLC1A2	NM_001439342.1		c.550-1826C>A		intron	N/A	NP_001426271.1
	SLC1A2	NM_001195728.3		c.535-1826C>A		intron	N/A	NP_001182657.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A2	ENST00000278379.9	TSL:1 MANE Select	c.562-1826C>A		intron	N/A	ENSP00000278379.3
	SLC1A2	ENST00000395750.6	TSL:1	c.550-1826C>A		intron	N/A	ENSP00000379099.2
	SLC1A2	ENST00000644779.1		c.673-1826C>A		intron	N/A	ENSP00000494258.1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30115 AN: 152048 Hom.: 3445 Cov.: 32

Gnomad AFR AF: 0.0837

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.198 AC: 30155 AN: 152166 Hom.: 3465 Cov.: 32 AF XY: 0.200 AC XY: 14883 AN XY: 74386

African (AFR) AF: 0.0835 AC: 3469 AN: 41532

American (AMR) AF: 0.272 AC: 4154 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 866 AN: 3468

East Asian (EAS) AF: 0.215 AC: 1114 AN: 5172

South Asian (SAS) AF: 0.104 AC: 500 AN: 4818

European-Finnish (FIN) AF: 0.293 AC: 3109 AN: 10600

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.239 AC: 16241 AN: 67970

Other (OTH) AF: 0.208 AC: 439 AN: 2112

Alfa AF: 0.229 Hom.: 17424

Bravo AF: 0.195

Asia WGS AF: 0.189 AC: 656 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.60
DANN	Benign	0.43
PhyloP100		-0.44
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: rs3794087; hg19: chr11-35329615;