rs4755404

chr11-35404103-G-Cchr11-35404103-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
SLC1A2	NM_004171.4	c.17+14847C>G		intron_variant		ENST00000278379.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC1A2	ENST00000278379.9	c.17+14847C>G		intron_variant		1	NM_004171.4	P4

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

Gnomad4 AFR AF: 0.470

Gnomad4 AMR AF: 0.634

Gnomad4 ASJ AF: 0.739

Gnomad4 EAS AF: 0.636

Gnomad4 SAS AF: 0.614

Gnomad4 FIN AF: 0.678

Gnomad4 NFE AF: 0.598

Gnomad4 OTH AF: 0.575

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

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

Publications

LitVar

Other links and lift over

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