rs928209

Variant names:

• chr9-4542890-A-G
• rs928209
• NM_004170.6:c.92-1677A>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.92-1677A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 152,066 control chromosomes in the GnomAD database, including 9,317 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 0.32 (9317 hom., cov: 32)
• Consequence: SLC1A1 NM_004170.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.815
• Publications: 6 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 (NFE) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A1	NM_004170.6	c.92-1677A>G		intron_variant	Intron 1 of 11	ENST00000262352.8	NP_004161.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A1	ENST00000262352.8	c.92-1677A>G		intron_variant	Intron 1 of 11	1	NM_004170.6	ENSP00000262352.3

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48722 AN: 151946 Hom.: 9315 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.360

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

GnomAD4 genome AF: 0.320 AC: 48726 AN: 152066 Hom.: 9317 Cov.: 32 AF XY: 0.317 AC XY: 23551 AN XY: 74320

African (AFR) AF: 0.118 AC: 4913 AN: 41548

American (AMR) AF: 0.418 AC: 6377 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1385 AN: 3468

East Asian (EAS) AF: 0.178 AC: 921 AN: 5182

South Asian (SAS) AF: 0.217 AC: 1046 AN: 4824

European-Finnish (FIN) AF: 0.397 AC: 4185 AN: 10550

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.423 AC: 28717 AN: 67908

Other (OTH) AF: 0.361 AC: 761 AN: 2108

Alfa AF: 0.386 Hom.: 7392

Bravo AF: 0.317

Asia WGS AF: 0.205 AC: 716 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	0.39
DANN	Benign	0.83
PhyloP100		-0.81
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: rs928209; hg19: chr9-4542890;