11-35303113-C-T

Variant names:

• chr11-35303113-C-T
• rs3794089
• NM_004171.4:c.731-1468G>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.731-1468G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 151,292 control chromosomes in the GnomAD database, including 9,939 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 0.34 (9939 hom., cov: 28)
• Consequence: SLC1A2 NM_004171.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 6 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A2	NM_004171.4	c.731-1468G>A		intron_variant	Intron 5 of 10	ENST00000278379.9	NP_004162.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A2	ENST00000278379.9	c.731-1468G>A		intron_variant	Intron 5 of 10	1	NM_004171.4	ENSP00000278379.3

Frequencies

GnomAD3 genomes AF: 0.342 AC: 51647 AN: 151174 Hom.: 9946 Cov.: 28

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.341 AC: 51632 AN: 151292 Hom.: 9939 Cov.: 28 AF XY: 0.349 AC XY: 25736 AN XY: 73806

African (AFR) AF: 0.164 AC: 6764 AN: 41204

American (AMR) AF: 0.357 AC: 5418 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 1679 AN: 3460

East Asian (EAS) AF: 0.524 AC: 2687 AN: 5128

South Asian (SAS) AF: 0.560 AC: 2662 AN: 4752

European-Finnish (FIN) AF: 0.349 AC: 3633 AN: 10412

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.404 AC: 27402 AN: 67852

Other (OTH) AF: 0.378 AC: 792 AN: 2096

Alfa AF: 0.392 Hom.: 20646

Bravo AF: 0.330

Asia WGS AF: 0.480 AC: 1666 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.97
DANN	Benign	0.26
PhyloP100		-1.2
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: rs3794089; hg19: chr11-35324660;