11-35393099-T-G

Variant names:

• chr11-35393099-T-G
• rs1570226
• NM_004171.4:c.17+25851A>C

Variant summary

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

The NM_004171.4(SLC1A2):​c.17+25851A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,060 control chromosomes in the GnomAD database, including 7,040 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 0.28 (7040 hom., cov: 31)
• Consequence: SLC1A2 NM_004171.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A2	NM_004171.4	c.17+25851A>C		intron_variant	Intron 1 of 10	ENST00000278379.9	NP_004162.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A2	ENST00000278379.9	c.17+25851A>C		intron_variant	Intron 1 of 10	1	NM_004171.4	ENSP00000278379.3

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41837 AN: 151942 Hom.: 7041 Cov.: 31

Gnomad AFR AF: 0.0727

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.285

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

GnomAD4 genome AF: 0.275 AC: 41834 AN: 152060 Hom.: 7040 Cov.: 31 AF XY: 0.279 AC XY: 20712 AN XY: 74306

African (AFR) AF: 0.0725 AC: 3011 AN: 41528

American (AMR) AF: 0.312 AC: 4770 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1297 AN: 3466

East Asian (EAS) AF: 0.317 AC: 1637 AN: 5162

South Asian (SAS) AF: 0.319 AC: 1535 AN: 4810

European-Finnish (FIN) AF: 0.377 AC: 3977 AN: 10560

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.363 AC: 24636 AN: 67954

Other (OTH) AF: 0.282 AC: 593 AN: 2106

Alfa AF: 0.338 Hom.: 17928

Bravo AF: 0.261

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.23
DANN	Benign	0.79
PhyloP100		-1.4
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: rs1570226; hg19: chr11-35414646;