rs10739062

Positions:

• chr9-4502848-C-G

Variant summary

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

The NM_004170.6(SLC1A1):​c.91+12078C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 151,376 control chromosomes in the GnomAD database, including 20,072 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 0.50 (20072 hom., cov: 32)
• Consequence: SLC1A1 NM_004170.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.893

Genes affected

SLC1A1 (HGNC:10939): (solute carrier family 1 member 1) This gene encodes a member of the high-affinity glutamate transporters that play an essential role in transporting glutamate across plasma membranes. In brain, these transporters are crucial in terminating the postsynaptic action of the neurotransmitter glutamate, and in maintaining extracellular glutamate concentrations below neurotoxic levels. This transporter also transports aspartate, and mutations in this gene are thought to cause dicarboxylicamino aciduria, also known as glutamate-aspartate transport defect. [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC1A1	NM_004170.6	c.91+12078C>G		intron_variant		ENST00000262352.8	NP_004161.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC1A1	ENST00000262352.8	c.91+12078C>G		intron_variant		1	NM_004170.6	ENSP00000262352.3

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75685 AN: 151254 Hom.: 20035 Cov.: 32

Gnomad AFR AF: 0.648

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.463

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

GnomAD4 genome AF: 0.501 AC: 75771 AN: 151376 Hom.: 20072 Cov.: 32 AF XY: 0.497 AC XY: 36779 AN XY: 74010

Gnomad4 AFR AF: 0.648

Gnomad4 AMR AF: 0.455

Gnomad4 ASJ AF: 0.430

Gnomad4 EAS AF: 0.591

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.445

Gnomad4 NFE AF: 0.441

Gnomad4 OTH AF: 0.461

Alfa AF: 0.475 Hom.: 2347

Bravo AF: 0.511

Asia WGS AF: 0.461 AC: 1600 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.59
DANN	Benign	0.38

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: rs10739062; hg19: chr9-4502848;