rs12361171

Positions:

• chr11-35256786-T-A
• chr11-35256786-T-C

Variant summary

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

The NM_004171.4(SLC1A2):​c.*4108A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 151,260 control chromosomes in the GnomAD database, including 9,473 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 (9473 hom., cov: 31)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: SLC1A2 NM_004171.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC1A2	NM_004171.4	c.*4108A>T		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	c.*4108A>T		3_prime_UTR_variant	11/11	1	NM_004171.4	ENSP00000278379.3
SLC1A2	ENST00000642769.1	c.*51-1978A>T		intron_variant				ENSP00000493843.1
SLC1A2	ENST00000647076.1	c.*51-1978A>T		intron_variant				ENSP00000496759.1
SLC1A2	ENST00000464522.2	c.220-1978A>T		intron_variant		3		ENSP00000435406.1

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50697 AN: 151140 Hom.: 9477 Cov.: 31

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.368

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.335 AC: 50693 AN: 151258 Hom.: 9473 Cov.: 31 AF XY: 0.341 AC XY: 25210 AN XY: 73822

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.351

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.474

Gnomad4 SAS AF: 0.536

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.367

Alfa AF: 0.363 Hom.: 1299

Bravo AF: 0.324

Asia WGS AF: 0.439 AC: 1526 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.0
DANN	Benign	0.49

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: rs12361171; hg19: chr11-35278333;