rs1043101

Positions:

• chr11-35253282-A-G
• chr11-35253282-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004171.4(SLC1A2):​c.*7612T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 152,396 control chromosomes in the GnomAD database, including 9,484 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 0.33 (9461 hom., cov: 32)
  • Exomes 𝑓: 0.34 (23 hom.)
• Consequence: SLC1A2 NM_004171.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.528

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC1A2	NM_004171.4	c.*7612T>C		3_prime_UTR_variant	11/11	ENST00000278379.9	NP_004162.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC1A2	ENST00000278379.9	c.*7612T>C		3_prime_UTR_variant	11/11	1	NM_004171.4	ENSP00000278379	P4
SLC1A2	ENST00000642769.1	c.*1577T>C		3_prime_UTR_variant	7/7			ENSP00000493843

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50700 AN: 151900 Hom.: 9465 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.368

GnomAD4 exome AF: 0.341 AC: 129 AN: 378 Hom.: 23 Cov.: 0 AF XY: 0.330 AC XY: 76 AN XY: 230

Gnomad4 FIN exome AF: 0.337

Gnomad4 NFE exome AF: 0.667

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.333 AC: 50696 AN: 152018 Hom.: 9461 Cov.: 32 AF XY: 0.339 AC XY: 25226 AN XY: 74332

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.464

Gnomad4 EAS AF: 0.472

Gnomad4 SAS AF: 0.535

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.398

Gnomad4 OTH AF: 0.366

Alfa AF: 0.372 Hom.: 8841

Bravo AF: 0.324

Asia WGS AF: 0.439 AC: 1525 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs1043101; hg19: chr11-35274829;