chr11-35251721-T-C

Variant names:

• chr11-35251721-T-C
• rs3088168
• NM_004171.4:c.*9173A>G

Variant summary

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

The NM_004171.4(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 NM_004171.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.293
• Publications: 22 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-AS1 (HGNC:40534): (SLC1A2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004171.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A2	NM_004171.4	MANE Select	c.*9173A>G		3_prime_UTR	Exon 11 of 11	NP_004162.2
	SLC1A2	NM_001439342.1		c.*9173A>G		3_prime_UTR	Exon 11 of 11	NP_001426271.1
	SLC1A2	NM_001195728.3		c.*9173A>G		3_prime_UTR	Exon 12 of 12	NP_001182657.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A2	ENST00000278379.9	TSL:1 MANE Select	c.*9173A>G		3_prime_UTR	Exon 11 of 11	ENSP00000278379.3
	SLC1A2	ENST00000642769.1		c.*3138A>G		3_prime_UTR	Exon 7 of 7	ENSP00000493843.1
	SLC1A2-AS1	ENST00000844195.1		n.426+13327T>C		intron	N/A

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.347 AC: 147 AN: 424

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AF: 0.250 AC: 1 AN: 4

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

African (AFR) AF: 0.150 AC: 6225 AN: 41466

American (AMR) AF: 0.350 AC: 5340 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1607 AN: 3466

East Asian (EAS) AF: 0.472 AC: 2441 AN: 5172

South Asian (SAS) AF: 0.536 AC: 2585 AN: 4822

European-Finnish (FIN) AF: 0.342 AC: 3604 AN: 10552

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.398 AC: 27029 AN: 67920

Other (OTH) AF: 0.361 AC: 763 AN: 2112

Alfa AF: 0.376 Hom.: 14741

Bravo AF: 0.320

Asia WGS AF: 0.440 AC: 1527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.81
DANN	Benign	0.67
PhyloP100		-0.29
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: rs3088168; hg19: chr11-35273268; COSMIC: COSV53522132; COSMIC: COSV53522132;