11-35371054-A-G

Position:

• chr11-35371054-A-G

Variant summary

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

The NM_004171.4(SLC1A2):​c.17+47896T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 984,178 control chromosomes in the GnomAD database, including 289,514 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 0.82 (51349 hom., cov: 31)
  • Exomes 𝑓: 0.76 (238165 hom.)
• Consequence: SLC1A2 NM_004171.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC1A2	NM_004171.4	c.17+47896T>C		intron_variant		ENST00000278379.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC1A2	ENST00000278379.9	c.17+47896T>C		intron_variant		1	NM_004171.4	P4

Frequencies

GnomAD3 genomes AF: 0.818 AC: 124280 AN: 151960 Hom.: 51307 Cov.: 31

Gnomad AFR AF: 0.913

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.844

Gnomad ASJ AF: 0.848

Gnomad EAS AF: 0.950

Gnomad SAS AF: 0.911

Gnomad FIN AF: 0.754

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.747

Gnomad OTH AF: 0.799

GnomAD4 exome AF: 0.755 AC: 628485 AN: 832100 Hom.: 238165 Cov.: 25 AF XY: 0.755 AC XY: 289976 AN XY: 384288

Gnomad4 AFR exome AF: 0.927

Gnomad4 AMR exome AF: 0.842

Gnomad4 ASJ exome AF: 0.862

Gnomad4 EAS exome AF: 0.956

Gnomad4 SAS exome AF: 0.900

Gnomad4 FIN exome AF: 0.777

Gnomad4 NFE exome AF: 0.746

Gnomad4 OTH exome AF: 0.784

GnomAD4 genome AF: 0.818 AC: 124376 AN: 152078 Hom.: 51349 Cov.: 31 AF XY: 0.822 AC XY: 61074 AN XY: 74320

Gnomad4 AFR AF: 0.913

Gnomad4 AMR AF: 0.844

Gnomad4 ASJ AF: 0.848

Gnomad4 EAS AF: 0.950

Gnomad4 SAS AF: 0.911

Gnomad4 FIN AF: 0.754

Gnomad4 NFE AF: 0.747

Gnomad4 OTH AF: 0.802

Alfa AF: 0.773 Hom.: 62982

Bravo AF: 0.830

Asia WGS AF: 0.905 AC: 3144 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs1885345; hg19: chr11-35392601;