chr11-35260921-C-T

Variant names:

• chr11-35260921-C-T
• rs114945303
• NM_004171.4:c.1698G>A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_004171.4(SLC1A2):​c.1698G>A​(p.Glu566Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000469 in 1,613,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0025 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00026 (0 hom.)
• Consequence: SLC1A2 NM_004171.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.161
• Publications: 0 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006164938).
• BP6: Variant 11-35260921-C-T is Benign according to our data. Variant chr11-35260921-C-T is described in ClinVar as Benign. ClinVar VariationId is 771955.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.161 with no splicing effect.

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.1698G>A	p.Glu566Glu	synonymous	Exon 11 of 11	NP_004162.2
	SLC1A2	NM_001439342.1		c.1686G>A	p.Glu562Glu	synonymous	Exon 11 of 11	NP_001426271.1
	SLC1A2	NM_001195728.3		c.1671G>A	p.Glu557Glu	synonymous	Exon 12 of 12	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.1698G>A	p.Glu566Glu	synonymous	Exon 11 of 11	ENSP00000278379.3	P43004-1
	SLC1A2	ENST00000395750.6	TSL:1	c.1686G>A	p.Glu562Glu	synonymous	Exon 11 of 11	ENSP00000379099.2	A0A2U3TZS7
	SLC1A2	ENST00000643134.1		c.1685G>A	p.Arg562Lys	missense	Exon 11 of 11	ENSP00000495188.1	A0A2R8Y6B8

Frequencies

GnomAD3 genomes AF: 0.00247 AC: 375 AN: 152120 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00836

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000982

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.000700 AC: 176 AN: 251436 AF XY: 0.000500

Gnomad AFR exome AF: 0.00966

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000615

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000261 AC: 382 AN: 1461468 Hom.: 0 Cov.: 29 AF XY: 0.000226 AC XY: 164 AN XY: 727080

African (AFR) AF: 0.00828 AC: 277 AN: 33470

American (AMR) AF: 0.000358 AC: 16 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5768

European-Non Finnish (NFE) AF: 0.0000504 AC: 56 AN: 1111638

Other (OTH) AF: 0.000447 AC: 27 AN: 60378

GnomAD4 genome AF: 0.00246 AC: 375 AN: 152238 Hom.: 0 Cov.: 33 AF XY: 0.00214 AC XY: 159 AN XY: 74436

African (AFR) AF: 0.00833 AC: 346 AN: 41534

American (AMR) AF: 0.000980 AC: 15 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 67996

Other (OTH) AF: 0.00427 AC: 9 AN: 2110

Alfa AF: 0.00118 Hom.: 0

Bravo AF: 0.00290

ESP6500AA AF: 0.00795 AC: 35

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000914 AC: 111

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	SLC1A2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_noAF	Benign	-0.47
CADD	Benign	5.0
DANN	Benign	0.79
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.15	T
MetaRNN	Benign	0.0062	T
PhyloP100		0.16
GERP RS		-0.42
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs114945303; hg19: chr11-35282468;