9-4551482-C-T

Position:

• chr9-4551482-C-T

Variant summary

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

The ENST00000262352.8(SLC1A1):​c.232+6775C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.904 in 152,272 control chromosomes in the GnomAD database, including 62,738 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 0.90 (62738 hom., cov: 32)
• Consequence: SLC1A1 ENST00000262352.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.663

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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC1A1	NM_004170.6	c.232+6775C>T		intron_variant		ENST00000262352.8	NP_004161.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC1A1	ENST00000262352.8	c.232+6775C>T		intron_variant		1	NM_004170.6	ENSP00000262352	P1

Frequencies

GnomAD3 genomes AF: 0.904 AC: 137517 AN: 152154 Hom.: 62707 Cov.: 32

Gnomad AFR AF: 0.769

Gnomad AMI AF: 0.979

Gnomad AMR AF: 0.944

Gnomad ASJ AF: 0.985

Gnomad EAS AF: 0.986

Gnomad SAS AF: 0.988

Gnomad FIN AF: 0.955

Gnomad MID AF: 0.978

Gnomad NFE AF: 0.950

Gnomad OTH AF: 0.921

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

GnomAD4 genome AF: 0.904 AC: 137610 AN: 152272 Hom.: 62738 Cov.: 32 AF XY: 0.907 AC XY: 67549 AN XY: 74456

Gnomad4 AFR AF: 0.769

Gnomad4 AMR AF: 0.944

Gnomad4 ASJ AF: 0.985

Gnomad4 EAS AF: 0.986

Gnomad4 SAS AF: 0.988

Gnomad4 FIN AF: 0.955

Gnomad4 NFE AF: 0.950

Gnomad4 OTH AF: 0.918

Alfa AF: 0.942 Hom.: 8595

Bravo AF: 0.898

Asia WGS AF: 0.973 AC: 3382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.81
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: rs2039216; hg19: chr9-4551482;