rs2273687

Variant names:

• chr11-35317346-G-C
• rs2273687
• NM_004171.4:c.157+31C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-35317346-G-C
• chr11-35317346-G-A
• chr11-35317346-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004171.4(SLC1A2):​c.157+31C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 1,602,160 control chromosomes in the GnomAD database, including 41,850 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3423 hom., cov: 32)
  • Exomes 𝑓: 0.23 (38427 hom.)
• Consequence: SLC1A2 NM_004171.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0770
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-35317346-G-C is Benign according to our data. Variant chr11-35317346-G-C is described in ClinVar as Benign. ClinVar VariationId is 1332978.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.262 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.157+31C>G		intron	N/A	NP_004162.2
	SLC1A2	NM_001439342.1		c.145+31C>G		intron	N/A	NP_001426271.1
	SLC1A2	NM_001195728.3		c.130+31C>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.157+31C>G		intron	N/A	ENSP00000278379.3	P43004-1
	SLC1A2	ENST00000395750.6	TSL:1	c.145+31C>G		intron	N/A	ENSP00000379099.2	A0A2U3TZS7
	SLC1A2	ENST00000644779.1		c.268+31C>G		intron	N/A	ENSP00000494258.1	A0A2R8YD46

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29664 AN: 152070 Hom.: 3404 Cov.: 32

Gnomad AFR AF: 0.0800

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.0933

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.195

GnomAD2 exomes AF: 0.219 AC: 53505 AN: 244394 AF XY: 0.213

Gnomad AFR exome AF: 0.0747

Gnomad AMR exome AF: 0.290

Gnomad ASJ exome AF: 0.259

Gnomad EAS exome AF: 0.202

Gnomad FIN exome AF: 0.279

Gnomad NFE exome AF: 0.237

Gnomad OTH exome AF: 0.249

GnomAD4 exome AF: 0.226 AC: 327107 AN: 1449972 Hom.: 38427 Cov.: 30 AF XY: 0.222 AC XY: 159654 AN XY: 719306

African (AFR) AF: 0.0762 AC: 2536 AN: 33278

American (AMR) AF: 0.285 AC: 12630 AN: 44300

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 6765 AN: 25942

East Asian (EAS) AF: 0.267 AC: 10497 AN: 39352

South Asian (SAS) AF: 0.103 AC: 8823 AN: 85770

European-Finnish (FIN) AF: 0.276 AC: 14609 AN: 53000

Middle Eastern (MID) AF: 0.215 AC: 1226 AN: 5714

European-Non Finnish (NFE) AF: 0.233 AC: 257376 AN: 1102836

Other (OTH) AF: 0.212 AC: 12645 AN: 59780

GnomAD4 genome AF: 0.195 AC: 29703 AN: 152188 Hom.: 3423 Cov.: 32 AF XY: 0.197 AC XY: 14657 AN XY: 74392

African (AFR) AF: 0.0798 AC: 3317 AN: 41554

American (AMR) AF: 0.269 AC: 4112 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 871 AN: 3472

East Asian (EAS) AF: 0.208 AC: 1073 AN: 5164

South Asian (SAS) AF: 0.0927 AC: 447 AN: 4820

European-Finnish (FIN) AF: 0.287 AC: 3041 AN: 10580

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16148 AN: 67988

Other (OTH) AF: 0.203 AC: 429 AN: 2112

Alfa AF: 0.151 Hom.: 453

Bravo AF: 0.191

Asia WGS AF: 0.181 AC: 629 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Developmental and epileptic encephalopathy, 41 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.37
PhyloP100		-0.077
PromoterAI		0.024	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: rs2273687;

hg19: chr11-35338893;

COSMIC: COSV53519249;

COSMIC: COSV53519249;