11-35419429-T-G

Position:

• chr11-35419429-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004171.4(SLC1A2):​c.-463A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 181,614 control chromosomes in the GnomAD database, including 27,522 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 0.54 (24311 hom., cov: 34)
  • Exomes 𝑓: 0.45 (3211 hom.)
• Consequence: SLC1A2 NM_004171.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.719

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC1A2	NM_004171.4	c.-463A>C		5_prime_UTR_variant	1/11	ENST00000278379.9	NP_004162.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC1A2	ENST00000278379.9	c.-463A>C		5_prime_UTR_variant	1/11	1	NM_004171.4	ENSP00000278379.3

Frequencies

GnomAD3 genomes AF: 0.540 AC: 82058 AN: 151948 Hom.: 24261 Cov.: 34

Gnomad AFR AF: 0.773

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.718

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.514

GnomAD4 exome AF: 0.452 AC: 13355 AN: 29556 Hom.: 3211 Cov.: 0 AF XY: 0.446 AC XY: 6809 AN XY: 15252

Gnomad4 AFR exome AF: 0.773

Gnomad4 AMR exome AF: 0.626

Gnomad4 ASJ exome AF: 0.492

Gnomad4 EAS exome AF: 0.767

Gnomad4 SAS exome AF: 0.445

Gnomad4 FIN exome AF: 0.395

Gnomad4 NFE exome AF: 0.396

Gnomad4 OTH exome AF: 0.488

GnomAD4 genome AF: 0.540 AC: 82165 AN: 152058 Hom.: 24311 Cov.: 34 AF XY: 0.540 AC XY: 40170 AN XY: 74324

Gnomad4 AFR AF: 0.773

Gnomad4 AMR AF: 0.588

Gnomad4 ASJ AF: 0.524

Gnomad4 EAS AF: 0.717

Gnomad4 SAS AF: 0.464

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.407

Gnomad4 OTH AF: 0.511

Alfa AF: 0.469 Hom.: 2767

Bravo AF: 0.568

Asia WGS AF: 0.581 AC: 2017 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	14
DANN	Benign	0.73

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4354668; hg19: chr11-35440976;