rs41352148

Variant names:

• chr11-35287989-T-C
• rs41352148
• NM_004171.4:c.1092-1038A>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.1092-1038A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,082 control chromosomes in the GnomAD database, including 5,230 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 0.26 (5230 hom., cov: 32)
• Consequence: SLC1A2 NM_004171.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.681
• 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 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 41

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen, G2P, Ambry Genetics
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.292 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.1092-1038A>G		intron	N/A	NP_004162.2
	SLC1A2	NM_001439342.1		c.1080-1038A>G		intron	N/A	NP_001426271.1
	SLC1A2	NM_001195728.3		c.1065-1038A>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.1092-1038A>G		intron	N/A	ENSP00000278379.3	P43004-1
	SLC1A2	ENST00000395750.6	TSL:1	c.1080-1038A>G		intron	N/A	ENSP00000379099.2	A0A2U3TZS7
	SLC1A2	ENST00000644779.1		c.1203-1038A>G		intron	N/A	ENSP00000494258.1	A0A2R8YD46

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39221 AN: 151964 Hom.: 5207 Cov.: 32

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.236

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

GnomAD4 genome AF: 0.258 AC: 39287 AN: 152082 Hom.: 5230 Cov.: 32 AF XY: 0.259 AC XY: 19226 AN XY: 74356

African (AFR) AF: 0.273 AC: 11303 AN: 41460

American (AMR) AF: 0.299 AC: 4573 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 713 AN: 3460

East Asian (EAS) AF: 0.211 AC: 1092 AN: 5180

South Asian (SAS) AF: 0.0995 AC: 480 AN: 4826

European-Finnish (FIN) AF: 0.319 AC: 3369 AN: 10574

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.250 AC: 16984 AN: 67990

Other (OTH) AF: 0.244 AC: 513 AN: 2104

Alfa AF: 0.257 Hom.: 833

Bravo AF: 0.259

Asia WGS AF: 0.202 AC: 699 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	11
DANN	Benign	0.88
PhyloP100		0.68
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: rs41352148;

hg19: chr11-35309536;