9-4546319-C-T

Variant names:

• chr9-4546319-C-T
• rs10758631
• NM_004170.6:c.232+1612C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_004170.6(SLC1A1):​c.232+1612C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00791 in 152,006 control chromosomes in the GnomAD database, including 15 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 0.0079 (15 hom., cov: 32)
• Consequence: SLC1A1 NM_004170.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.259
• Publications: 4 publications found

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]

SLC1A1 Gene-Disease associations (from GenCC):

• dicarboxylic aminoaciduria

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, PanelApp Australia
• hot water reflex epilepsy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BS2: High Homozygotes in GnomAd4 at 15 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004170.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A1	NM_004170.6	MANE Select	c.232+1612C>T		intron	N/A	NP_004161.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A1	ENST00000262352.8	TSL:1 MANE Select	c.232+1612C>T		intron	N/A	ENSP00000262352.3	P43005
	SLC1A1	ENST00000931882.1		c.232+1612C>T		intron	N/A	ENSP00000601941.1
	SLC1A1	ENST00000954075.1		c.92-15130C>T		intron	N/A	ENSP00000624134.1

Frequencies

GnomAD3 genomes AF: 0.00791 AC: 1201 AN: 151888 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.00232

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.00596

Gnomad ASJ AF: 0.0565

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00853

Gnomad FIN AF: 0.00398

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0100

Gnomad OTH AF: 0.0139

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

GnomAD4 genome AF: 0.00791 AC: 1202 AN: 152006 Hom.: 15 Cov.: 32 AF XY: 0.00782 AC XY: 581 AN XY: 74288

African (AFR) AF: 0.00232 AC: 96 AN: 41414

American (AMR) AF: 0.00595 AC: 91 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0565 AC: 196 AN: 3470

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5174

South Asian (SAS) AF: 0.00874 AC: 42 AN: 4804

European-Finnish (FIN) AF: 0.00398 AC: 42 AN: 10542

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0100 AC: 680 AN: 67992

Other (OTH) AF: 0.0137 AC: 29 AN: 2114

Alfa AF: 0.000208 Hom.: 25842

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.7
DANN	Benign	0.94
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs10758631; hg19: chr9-4546319;