rs10758631

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr9-4546319-C-A
• chr9-4546319-C-T

Variant summary

Our verdict is Benign. The variant received -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
• 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, LIMITED Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
• hot water reflex epilepsy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

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

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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A1	ENST00000262352.8	TSL:1 MANE Select	c.232+1612C>A		intron	N/A	ENSP00000262352.3

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

African (AFR) AF: 0.494 AC: 20460 AN: 41400

American (AMR) AF: 0.474 AC: 7237 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 1716 AN: 3470

East Asian (EAS) AF: 0.175 AC: 906 AN: 5172

South Asian (SAS) AF: 0.308 AC: 1477 AN: 4802

European-Finnish (FIN) AF: 0.427 AC: 4503 AN: 10538

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.440 AC: 29923 AN: 67982

Other (OTH) AF: 0.455 AC: 961 AN: 2114

Alfa AF: 0.450 Hom.: 25842

Bravo AF: 0.459

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.55
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

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;