chr9-4546319-C-A

Position:

• chr9-4546319-C-A

Variant summary

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

The NM_004170.6(SLC1A1):​c.232+1612C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 151,962 control chromosomes in the GnomAD database, including 15,417 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 (15417 hom., cov: 32)
• Consequence: SLC1A1 NM_004170.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.259

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC1A1	NM_004170.6	c.232+1612C>A		intron_variant		ENST00000262352.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC1A1	ENST00000262352.8	c.232+1612C>A		intron_variant		1	NM_004170.6	P1

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67789 AN: 151844 Hom.: 15413 Cov.: 32

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.460

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

GnomAD4 genome AF: 0.446 AC: 67812 AN: 151962 Hom.: 15417 Cov.: 32 AF XY: 0.440 AC XY: 32642 AN XY: 74264

Gnomad4 AFR AF: 0.494

Gnomad4 AMR AF: 0.474

Gnomad4 ASJ AF: 0.495

Gnomad4 EAS AF: 0.175

Gnomad4 SAS AF: 0.308

Gnomad4 FIN AF: 0.427

Gnomad4 NFE AF: 0.440

Gnomad4 OTH AF: 0.455

Alfa AF: 0.446 Hom.: 20030

Bravo AF: 0.459

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.55

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: rs10758631; hg19: chr9-4546319;