11-35265953-T-C

Variant names:

• chr11-35265953-T-C
• rs10836358
• NM_004171.4:c.1422-195A>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.1422-195A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,216 control chromosomes in the GnomAD database, including 1,121 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 0.12 (1121 hom., cov: 32)
• Consequence: SLC1A2 NM_004171.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.729
• Publications: 2 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.173 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A2	NM_004171.4	MANE Select	c.1422-195A>G		intron	N/A	NP_004162.2
	SLC1A2	NM_001439342.1		c.1410-195A>G		intron	N/A	NP_001426271.1
	SLC1A2	NM_001195728.3		c.1395-195A>G		intron	N/A	NP_001182657.1	P43004-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A2	ENST00000278379.9	TSL:1 MANE Select	c.1422-195A>G		intron	N/A	ENSP00000278379.3	P43004-1
	SLC1A2	ENST00000395750.6	TSL:1	c.1410-195A>G		intron	N/A	ENSP00000379099.2	A0A2U3TZS7
	SLC1A2	ENST00000644779.1		c.1533-195A>G		intron	N/A	ENSP00000494258.1	A0A2R8YD46

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17579 AN: 152098 Hom.: 1105 Cov.: 32

Gnomad AFR AF: 0.0689

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.0682

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.116 AC: 17626 AN: 152216 Hom.: 1121 Cov.: 32 AF XY: 0.117 AC XY: 8698 AN XY: 74422

African (AFR) AF: 0.0691 AC: 2870 AN: 41544

American (AMR) AF: 0.178 AC: 2731 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 427 AN: 3468

East Asian (EAS) AF: 0.152 AC: 788 AN: 5176

South Asian (SAS) AF: 0.0678 AC: 327 AN: 4822

European-Finnish (FIN) AF: 0.133 AC: 1408 AN: 10584

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8698 AN: 68008

Other (OTH) AF: 0.134 AC: 283 AN: 2108

Alfa AF: 0.115 Hom.: 196

Bravo AF: 0.119

Asia WGS AF: 0.150 AC: 521 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.9
DANN	Benign	0.71
PhyloP100		0.73
PromoterAI		0.0052	Neutral
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10836358;

hg19: chr11-35287500;