chr9-4542803-A-C

Variant names:

• chr9-4542803-A-C
• rs10491731
• NM_004170.6:c.92-1764A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004170.6(SLC1A1):​c.92-1764A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,246 control chromosomes in the GnomAD database, including 1,204 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 0.11 (1204 hom., cov: 32)
• Consequence: SLC1A1 NM_004170.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.207
• 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, 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.289 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A1	NM_004170.6	MANE Select	c.92-1764A>C		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.92-1764A>C		intron	N/A	ENSP00000262352.3	P43005
	SLC1A1	ENST00000931882.1		c.92-1764A>C		intron	N/A	ENSP00000601941.1
	SLC1A1	ENST00000954075.1		c.92-18646A>C		intron	N/A	ENSP00000624134.1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16126 AN: 152128 Hom.: 1206 Cov.: 32

Gnomad AFR AF: 0.0211

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.106 AC: 16122 AN: 152246 Hom.: 1204 Cov.: 32 AF XY: 0.112 AC XY: 8316 AN XY: 74434

African (AFR) AF: 0.0211 AC: 876 AN: 41582

American (AMR) AF: 0.112 AC: 1718 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 559 AN: 3468

East Asian (EAS) AF: 0.248 AC: 1283 AN: 5182

South Asian (SAS) AF: 0.302 AC: 1452 AN: 4814

European-Finnish (FIN) AF: 0.150 AC: 1591 AN: 10590

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8128 AN: 67992

Other (OTH) AF: 0.124 AC: 262 AN: 2112

Alfa AF: 0.126 Hom.: 822

Bravo AF: 0.0961

Asia WGS AF: 0.253 AC: 878 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.8
DANN	Benign	0.80
PhyloP100		0.21
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: rs10491731; hg19: chr9-4542803; COSMIC: COSV52051311;