rs7022369

Variant names:

• chr9-4527752-C-G
• rs7022369
• NM_004170.6:c.92-16815C>G

Your query was ambiguous. Multiple possible variants found:

• chr9-4527752-C-G
• chr9-4527752-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.92-16815C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 151,792 control chromosomes in the GnomAD database, including 15,871 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 (15871 hom., cov: 31)
• Consequence: SLC1A1 NM_004170.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.199
• Publications: 7 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=-1.05).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A1	NM_004170.6	c.92-16815C>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.92-16815C>G		intron_variant	Intron 1 of 11	1	NM_004170.6	ENSP00000262352.3

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67860 AN: 151672 Hom.: 15872 Cov.: 31

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.447 AC: 67881 AN: 151792 Hom.: 15871 Cov.: 31 AF XY: 0.441 AC XY: 32715 AN XY: 74154

African (AFR) AF: 0.353 AC: 14610 AN: 41376

American (AMR) AF: 0.501 AC: 7646 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 1683 AN: 3466

East Asian (EAS) AF: 0.198 AC: 1013 AN: 5126

South Asian (SAS) AF: 0.291 AC: 1402 AN: 4810

European-Finnish (FIN) AF: 0.488 AC: 5126 AN: 10512

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.513 AC: 34862 AN: 67944

Other (OTH) AF: 0.465 AC: 976 AN: 2100

Alfa AF: 0.468 Hom.: 2040

Bravo AF: 0.446

Asia WGS AF: 0.251 AC: 873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.82
DANN	Benign	0.62
PhyloP100		-0.20
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: rs7022369; hg19: chr9-4527752;