chr11-35265953-T-C

Position:

• chr11-35265953-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004171.4(SLC1A2):​c.1422-195A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,216 control chromosomes in the GnomAD database, including 1,121 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 0.12 (1121 hom., cov: 32)
• Consequence: SLC1A2 NM_004171.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.729

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC1A2	NM_004171.4	c.1422-195A>G		intron_variant		ENST00000278379.9	NP_004162.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC1A2	ENST00000278379.9	c.1422-195A>G		intron_variant		1	NM_004171.4	ENSP00000278379.3

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17579 AN: 152098 Hom.: 1105 Cov.: 32

Gnomad AFR AF: 0.0689

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.0682

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.116 AC: 17626 AN: 152216 Hom.: 1121 Cov.: 32 AF XY: 0.117 AC XY: 8698 AN XY: 74422

Gnomad4 AFR AF: 0.0691

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.0678

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.134

Alfa AF: 0.115 Hom.: 196

Bravo AF: 0.119

Asia WGS AF: 0.150 AC: 521 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.9
DANN	Benign	0.71

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: rs10836358; hg19: chr11-35287500;