NM_004171.4:c.*2785T>G

Variant names:

• chr11-35258109-A-C
• rs10768121
• NM_004171.4:c.*2785T>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.*2785T>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 0.326 in 152,194 control chromosomes in the GnomAD database, including 9,303 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 (9303 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC1A2 NM_004171.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.317
• Publications: 13 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=-0.87).
• 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.*2785T>G		3_prime_UTR	Exon 11 of 11	NP_004162.2
	SLC1A2	NM_001439342.1		c.*2785T>G		3_prime_UTR	Exon 11 of 11	NP_001426271.1
	SLC1A2	NM_001195728.3		c.*2785T>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.*2785T>G		3_prime_UTR	Exon 11 of 11	ENSP00000278379.3
	SLC1A2	ENST00000395750.6	TSL:1	c.*2785T>G		3_prime_UTR	Exon 11 of 11	ENSP00000379099.2
	SLC1A2	ENST00000479543.2	TSL:5	n.4062T>G		non_coding_transcript_exon	Exon 8 of 8

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49680 AN: 152076 Hom.: 9308 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.361

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

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) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

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

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.326 AC: 49673 AN: 152194 Hom.: 9303 Cov.: 32 AF XY: 0.333 AC XY: 24740 AN XY: 74386

African (AFR) AF: 0.138 AC: 5719 AN: 41542

American (AMR) AF: 0.346 AC: 5296 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1611 AN: 3472

East Asian (EAS) AF: 0.472 AC: 2444 AN: 5180

South Asian (SAS) AF: 0.535 AC: 2571 AN: 4808

European-Finnish (FIN) AF: 0.342 AC: 3615 AN: 10580

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

European-Non Finnish (NFE) AF: 0.398 AC: 27064 AN: 68000

Other (OTH) AF: 0.359 AC: 759 AN: 2114

Alfa AF: 0.372 Hom.: 6599

Bravo AF: 0.316

Asia WGS AF: 0.438 AC: 1520 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.47
PhyloP100		-0.32
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: rs10768121; hg19: chr11-35279656;