rs10491731

Positions:

• chr9-4542803-A-C
• chr9-4542803-A-G

Variant summary

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

The NM_004170.6(SLC1A1):​c.92-1764A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,246 control chromosomes in the GnomAD database, including 1,204 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 0.11 (1204 hom., cov: 32)
• Consequence: SLC1A1 NM_004170.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.207

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A1	NM_004170.6	c.92-1764A>C		intron_variant	Intron 1 of 11	ENST00000262352.8	NP_004161.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A1	ENST00000262352.8	c.92-1764A>C		intron_variant	Intron 1 of 11	1	NM_004170.6	ENSP00000262352.3

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16126 AN: 152128 Hom.: 1206 Cov.: 32

Gnomad AFR AF: 0.0211

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.106 AC: 16122 AN: 152246 Hom.: 1204 Cov.: 32 AF XY: 0.112 AC XY: 8316 AN XY: 74434

Gnomad4 AFR AF: 0.0211

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.248

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.124

Alfa AF: 0.127 Hom.: 764

Bravo AF: 0.0961

Asia WGS AF: 0.253 AC: 878 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.8
DANN	Benign	0.80

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: rs10491731; hg19: chr9-4542803; COSMIC: COSV52051311;