9-4527752-C-G

Position:

• chr9-4527752-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.92-16815C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 151,792 control chromosomes in the GnomAD database, including 15,871 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 0.45 (15871 hom., cov: 31)
• Consequence: SLC1A1 NM_004170.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.199

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=-1.05).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC1A1	NM_004170.6	c.92-16815C>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.92-16815C>G		intron_variant		1	NM_004170.6	ENSP00000262352	P1

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67860 AN: 151672 Hom.: 15872 Cov.: 31

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.447 AC: 67881 AN: 151792 Hom.: 15871 Cov.: 31 AF XY: 0.441 AC XY: 32715 AN XY: 74154

Gnomad4 AFR AF: 0.353

Gnomad4 AMR AF: 0.501

Gnomad4 ASJ AF: 0.486

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.291

Gnomad4 FIN AF: 0.488

Gnomad4 NFE AF: 0.513

Gnomad4 OTH AF: 0.465

Alfa AF: 0.468 Hom.: 2040

Bravo AF: 0.446

Asia WGS AF: 0.251 AC: 873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.82
DANN	Benign	0.62

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: rs7022369; hg19: chr9-4527752;