rs56205617

Positions:

• chr11-35322560-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001195728.3(SLC1A2):​c.-11+1G>A variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0295 in 1,516,772 control chromosomes in the GnomAD database, including 761 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.033 (95 hom., cov: 32)
  • Exomes 𝑓: 0.029 (666 hom.)
• Consequence: SLC1A2 NM_001195728.3 splice_donor, intron
• Scores: Splicing: ADA: 0.00006553
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 11-35322560-C-T is Benign according to our data. Variant chr11-35322560-C-T is described in Lovd as [Likely_benign].
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC1A2	NM_004171.4	c.18-5044G>A		intron_variant		ENST00000278379.9	NP_004162.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC1A2	ENST00000278379.9	c.18-5044G>A		intron_variant		1	NM_004171.4	ENSP00000278379.3

Frequencies

GnomAD3 genomes AF: 0.0333 AC: 5063 AN: 152162 Hom.: 95 Cov.: 32

Gnomad AFR AF: 0.0433

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.0285

Gnomad ASJ AF: 0.0499

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0147

Gnomad FIN AF: 0.0260

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0313

Gnomad OTH AF: 0.0377

GnomAD3 exomes AF: 0.0263 AC: 3368 AN: 127894 Hom.: 57 AF XY: 0.0260 AC XY: 1818 AN XY: 70036

Gnomad AFR exome AF: 0.0460

Gnomad AMR exome AF: 0.0203

Gnomad ASJ exome AF: 0.0428

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0168

Gnomad FIN exome AF: 0.0304

Gnomad NFE exome AF: 0.0330

Gnomad OTH exome AF: 0.0377

GnomAD4 exome AF: 0.0290 AC: 39620 AN: 1364492 Hom.: 666 Cov.: 27 AF XY: 0.0290 AC XY: 19533 AN XY: 674592

Gnomad4 AFR exome AF: 0.0468

Gnomad4 AMR exome AF: 0.0209

Gnomad4 ASJ exome AF: 0.0458

Gnomad4 EAS exome AF: 0.0000281

Gnomad4 SAS exome AF: 0.0162

Gnomad4 FIN exome AF: 0.0300

Gnomad4 NFE exome AF: 0.0299

Gnomad4 OTH exome AF: 0.0330

GnomAD4 genome AF: 0.0333 AC: 5065 AN: 152280 Hom.: 95 Cov.: 32 AF XY: 0.0327 AC XY: 2434 AN XY: 74454

Gnomad4 AFR AF: 0.0432

Gnomad4 AMR AF: 0.0285

Gnomad4 ASJ AF: 0.0499

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0147

Gnomad4 FIN AF: 0.0260

Gnomad4 NFE AF: 0.0313

Gnomad4 OTH AF: 0.0378

Alfa AF: 0.0335 Hom.: 16

Bravo AF: 0.0341

TwinsUK AF: 0.0272 AC: 101

ALSPAC AF: 0.0324 AC: 125

ExAC AF: 0.0188 AC: 309

Asia WGS AF: 0.00866 AC: 30 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.076
DANN	Benign	0.42
FATHMM_MKL	Benign	0.0020	N
GERP RS		-4.7

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000066
dbscSNV1_RF	Benign	0.020
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: rs56205617; hg19: chr11-35344107;