chr11-35251721-T-C

Position:

• chr11-35251721-T-C

Variant summary

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

The ENST00000278379.9(SLC1A2):​c.*9173A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 152,412 control chromosomes in the GnomAD database, including 9,401 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 (9375 hom., cov: 32)
  • Exomes 𝑓: 0.35 (26 hom.)
• Consequence: SLC1A2 ENST00000278379.9 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.293

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=-0.82).
• 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.*9173A>G		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.*9173A>G		3_prime_UTR_variant	11/11	1	NM_004171.4	ENSP00000278379	P4
SLC1A2	ENST00000642769.1	c.*3138A>G		3_prime_UTR_variant	7/7			ENSP00000493843

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50187 AN: 151864 Hom.: 9380 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.363

GnomAD4 exome AF: 0.349 AC: 150 AN: 430 Hom.: 26 Cov.: 0 AF XY: 0.333 AC XY: 86 AN XY: 258

Gnomad4 FIN exome AF: 0.347

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.330 AC: 50186 AN: 151982 Hom.: 9375 Cov.: 32 AF XY: 0.337 AC XY: 25015 AN XY: 74314

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.464

Gnomad4 EAS AF: 0.472

Gnomad4 SAS AF: 0.536

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.398

Gnomad4 OTH AF: 0.361

Alfa AF: 0.385 Hom.: 11777

Bravo AF: 0.320

Asia WGS AF: 0.440 AC: 1527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.81
DANN	Benign	0.67

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: rs3088168; hg19: chr11-35273268; COSMIC: COSV53522132; COSMIC: COSV53522132;