9-4490880-T-C

Position:

• chr9-4490880-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004170.6(SLC1A1):​c.91+110T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.756 in 879,400 control chromosomes in the GnomAD database, including 252,840 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.72 (40059 hom., cov: 33)
  • Exomes 𝑓: 0.76 (212781 hom.)
• Consequence: SLC1A1 NM_004170.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.833

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 9-4490880-T-C is Benign according to our data. Variant chr9-4490880-T-C is described in ClinVar as [Benign]. Clinvar id is 1264590.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC1A1	NM_004170.6	c.91+110T>C		intron_variant		ENST00000262352.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC1A1	ENST00000262352.8	c.91+110T>C		intron_variant		1	NM_004170.6	P1

Frequencies

GnomAD3 genomes AF: 0.722 AC: 109617 AN: 151864 Hom.: 40040 Cov.: 33

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.828

Gnomad AMR AF: 0.759

Gnomad ASJ AF: 0.790

Gnomad EAS AF: 0.792

Gnomad SAS AF: 0.721

Gnomad FIN AF: 0.771

Gnomad MID AF: 0.885

Gnomad NFE AF: 0.770

Gnomad OTH AF: 0.773

GnomAD4 exome AF: 0.763 AC: 555204 AN: 727418 Hom.: 212781 AF XY: 0.763 AC XY: 289081 AN XY: 378812

Gnomad4 AFR exome AF: 0.592

Gnomad4 AMR exome AF: 0.741

Gnomad4 ASJ exome AF: 0.789

Gnomad4 EAS exome AF: 0.819

Gnomad4 SAS exome AF: 0.724

Gnomad4 FIN exome AF: 0.769

Gnomad4 NFE exome AF: 0.770

Gnomad4 OTH exome AF: 0.770

GnomAD4 genome AF: 0.722 AC: 109680 AN: 151982 Hom.: 40059 Cov.: 33 AF XY: 0.725 AC XY: 53827 AN XY: 74290

Gnomad4 AFR AF: 0.596

Gnomad4 AMR AF: 0.758

Gnomad4 ASJ AF: 0.790

Gnomad4 EAS AF: 0.792

Gnomad4 SAS AF: 0.721

Gnomad4 FIN AF: 0.771

Gnomad4 NFE AF: 0.770

Gnomad4 OTH AF: 0.777

Alfa AF: 0.681 Hom.: 2342

Bravo AF: 0.718

Asia WGS AF: 0.746 AC: 2594 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.8
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: rs12002726; hg19: chr9-4490880;