11-35268272-A-G

Variant names:

• chr11-35268272-A-G
• rs1570214
• NM_004171.4:c.1422-2514T>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.1422-2514T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 152,066 control chromosomes in the GnomAD database, including 11,122 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 0.38 (11122 hom., cov: 32)
• Consequence: SLC1A2 NM_004171.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.359
• Publications: 5 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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.516 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.1422-2514T>C		intron	N/A	NP_004162.2
	SLC1A2	NM_001439342.1		c.1410-2514T>C		intron	N/A	NP_001426271.1
	SLC1A2	NM_001195728.3		c.1395-2514T>C		intron	N/A	NP_001182657.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A2	ENST00000278379.9	TSL:1 MANE Select	c.1422-2514T>C		intron	N/A	ENSP00000278379.3
	SLC1A2	ENST00000395750.6	TSL:1	c.1410-2514T>C		intron	N/A	ENSP00000379099.2
	SLC1A2	ENST00000644779.1		c.1533-2514T>C		intron	N/A	ENSP00000494258.1

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57570 AN: 151946 Hom.: 11119 Cov.: 32

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.397

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.379 AC: 57599 AN: 152066 Hom.: 11122 Cov.: 32 AF XY: 0.383 AC XY: 28495 AN XY: 74328

African (AFR) AF: 0.325 AC: 13476 AN: 41452

American (AMR) AF: 0.367 AC: 5605 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1612 AN: 3472

East Asian (EAS) AF: 0.432 AC: 2230 AN: 5160

South Asian (SAS) AF: 0.533 AC: 2571 AN: 4820

European-Finnish (FIN) AF: 0.342 AC: 3616 AN: 10570

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

European-Non Finnish (NFE) AF: 0.398 AC: 27064 AN: 67992

Other (OTH) AF: 0.394 AC: 831 AN: 2108

Alfa AF: 0.402 Hom.: 6527

Bravo AF: 0.374

Asia WGS AF: 0.441 AC: 1530 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.59
DANN	Benign	0.74
PhyloP100		-0.36
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: rs1570214; hg19: chr11-35289819;