rs10739062

Variant names:

• chr9-4502848-C-G
• rs10739062
• NM_004170.6:c.91+12078C>G

Your query was ambiguous. Multiple possible variants found:

• chr9-4502848-C-G
• chr9-4502848-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.91+12078C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 151,376 control chromosomes in the GnomAD database, including 20,072 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 0.50 (20072 hom., cov: 32)
• Consequence: SLC1A1 NM_004170.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.893
• Publications: 9 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A1	NM_004170.6	c.91+12078C>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.91+12078C>G		intron_variant	Intron 1 of 11	1	NM_004170.6	ENSP00000262352.3

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75685 AN: 151254 Hom.: 20035 Cov.: 32

Gnomad AFR AF: 0.648

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.463

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

GnomAD4 genome AF: 0.501 AC: 75771 AN: 151376 Hom.: 20072 Cov.: 32 AF XY: 0.497 AC XY: 36779 AN XY: 74010

African (AFR) AF: 0.648 AC: 26516 AN: 40898

American (AMR) AF: 0.455 AC: 6928 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.430 AC: 1492 AN: 3470

East Asian (EAS) AF: 0.591 AC: 3055 AN: 5168

South Asian (SAS) AF: 0.350 AC: 1684 AN: 4814

European-Finnish (FIN) AF: 0.445 AC: 4695 AN: 10548

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.441 AC: 29963 AN: 67940

Other (OTH) AF: 0.461 AC: 972 AN: 2108

Alfa AF: 0.475 Hom.: 2347

Bravo AF: 0.511

Asia WGS AF: 0.461 AC: 1600 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.59
DANN	Benign	0.38
PhyloP100		-0.89
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: rs10739062; hg19: chr9-4502848;