9-4547288-A-G

Variant names:

• chr9-4547288-A-G
• rs10815019
• NM_004170.6:c.232+2581A>G

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+2581A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 152,140 control chromosomes in the GnomAD database, including 9,544 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 0.35 (9544 hom., cov: 33)
• Consequence: SLC1A1 NM_004170.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A1	NM_004170.6	c.232+2581A>G		intron_variant	Intron 2 of 11	ENST00000262352.8	NP_004161.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A1	ENST00000262352.8	c.232+2581A>G		intron_variant	Intron 2 of 11	1	NM_004170.6	ENSP00000262352.3

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52674 AN: 152022 Hom.: 9515 Cov.: 33

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.336

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

GnomAD4 genome AF: 0.347 AC: 52750 AN: 152140 Hom.: 9544 Cov.: 33 AF XY: 0.345 AC XY: 25628 AN XY: 74376

African (AFR) AF: 0.453 AC: 18781 AN: 41470

American (AMR) AF: 0.272 AC: 4152 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1078 AN: 3470

East Asian (EAS) AF: 0.229 AC: 1185 AN: 5180

South Asian (SAS) AF: 0.376 AC: 1815 AN: 4824

European-Finnish (FIN) AF: 0.321 AC: 3396 AN: 10572

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.311 AC: 21170 AN: 68012

Other (OTH) AF: 0.341 AC: 720 AN: 2114

Alfa AF: 0.312 Hom.: 16155

Bravo AF: 0.343

Asia WGS AF: 0.342 AC: 1190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	13
DANN	Benign	0.75
PhyloP100		0.064
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: rs10815019; hg19: chr9-4547288; COSMIC: COSV52051351;