rs4755404

Variant names:

• chr11-35404103-G-C
• rs4755404
• NM_004171.4:c.17+14847C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-35404103-G-C
• chr11-35404103-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004171.4(SLC1A2):​c.17+14847C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 151,772 control chromosomes in the GnomAD database, including 25,594 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 0.58 (25594 hom., cov: 30)
• Consequence: SLC1A2 NM_004171.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.680
• Publications: 10 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: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A2	NM_004171.4	c.17+14847C>G		intron_variant	Intron 1 of 10	ENST00000278379.9	NP_004162.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A2	ENST00000278379.9	c.17+14847C>G		intron_variant	Intron 1 of 10	1	NM_004171.4	ENSP00000278379.3

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87441 AN: 151654 Hom.: 25571 Cov.: 30

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.739

Gnomad EAS AF: 0.636

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.678

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.573

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

GnomAD4 genome AF: 0.577 AC: 87503 AN: 151772 Hom.: 25594 Cov.: 30 AF XY: 0.583 AC XY: 43228 AN XY: 74126

African (AFR) AF: 0.470 AC: 19428 AN: 41364

American (AMR) AF: 0.634 AC: 9694 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.739 AC: 2564 AN: 3470

East Asian (EAS) AF: 0.636 AC: 3242 AN: 5100

South Asian (SAS) AF: 0.614 AC: 2944 AN: 4798

European-Finnish (FIN) AF: 0.678 AC: 7144 AN: 10534

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.598 AC: 40624 AN: 67916

Other (OTH) AF: 0.575 AC: 1212 AN: 2106

Alfa AF: 0.582 Hom.: 3252

Bravo AF: 0.570

Asia WGS AF: 0.585 AC: 2034 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.2
DANN	Benign	0.58
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

Other links and lift over

dbSNP: rs4755404; hg19: chr11-35425650; COSMIC: COSV53525127;