11-35259305-A-G

Variant names:

• chr11-35259305-A-G
• rs10768122
• NM_004171.4:c.*1589T>C

Variant summary

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

The NM_004171.4(SLC1A2):​c.*1589T>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 152,464 control chromosomes in the GnomAD database, including 9,517 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 (9495 hom., cov: 32)
  • Exomes 𝑓: 0.34 (22 hom.)
• Consequence: SLC1A2 NM_004171.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.181
• Publications: 36 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.518 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.*1589T>C		3_prime_UTR	Exon 11 of 11	NP_004162.2
	SLC1A2	NM_001439342.1		c.*1589T>C		3_prime_UTR	Exon 11 of 11	NP_001426271.1
	SLC1A2	NM_001195728.3		c.*1589T>C		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.*1589T>C		3_prime_UTR	Exon 11 of 11	ENSP00000278379.3
	SLC1A2	ENST00000395750.6	TSL:1	c.*1589T>C		3_prime_UTR	Exon 11 of 11	ENSP00000379099.2
	SLC1A2	ENST00000479543.2	TSL:5	n.2866T>C		non_coding_transcript_exon	Exon 8 of 8

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50781 AN: 151932 Hom.: 9498 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.366

GnomAD4 exome AF: 0.340 AC: 140 AN: 412 Hom.: 22 Cov.: 0 AF XY: 0.329 AC XY: 81 AN XY: 246

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.342 AC: 138 AN: 404

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

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

GnomAD4 genome AF: 0.334 AC: 50779 AN: 152052 Hom.: 9495 Cov.: 32 AF XY: 0.340 AC XY: 25264 AN XY: 74334

African (AFR) AF: 0.163 AC: 6748 AN: 41480

American (AMR) AF: 0.349 AC: 5335 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1610 AN: 3468

East Asian (EAS) AF: 0.473 AC: 2445 AN: 5174

South Asian (SAS) AF: 0.535 AC: 2577 AN: 4816

European-Finnish (FIN) AF: 0.342 AC: 3620 AN: 10574

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.398 AC: 27080 AN: 67964

Other (OTH) AF: 0.365 AC: 768 AN: 2104

Alfa AF: 0.383 Hom.: 52669

Bravo AF: 0.324

Asia WGS AF: 0.439 AC: 1526 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.0
DANN	Benign	0.39
PhyloP100		0.18
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs10768122; hg19: chr11-35280852;