rs7858819

Variant names:

• chr9-4559892-C-T
• rs7858819
• NM_004170.6:c.233-1557C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004170.6(SLC1A1):​c.233-1557C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 152,078 control chromosomes in the GnomAD database, including 5,144 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 0.25 (5144 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC1A1 NM_004170.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.400

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]

SPATA6L (HGNC:25472): (spermatogenesis associated 6 like) Predicted to enable myosin light chain binding activity. Predicted to be involved in spermatogenesis. Predicted to be located in sperm connecting piece. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A1	NM_004170.6	c.233-1557C>T		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.233-1557C>T		intron_variant	Intron 2 of 11	1	NM_004170.6	ENSP00000262352.3
SLC1A1	ENST00000490167.1	n.88C>T		non_coding_transcript_exon_variant	Exon 1 of 3	3
SPATA6L	ENST00000485616.5	n.*782-5504G>A		intron_variant	Intron 12 of 12	2		ENSP00000420003.1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37909 AN: 151960 Hom.: 5138 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.227

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.249 AC: 37932 AN: 152078 Hom.: 5144 Cov.: 32 AF XY: 0.255 AC XY: 18973 AN XY: 74328

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.463

Gnomad4 SAS AF: 0.185

Gnomad4 FIN AF: 0.384

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.225

Alfa AF: 0.243 Hom.: 572

Bravo AF: 0.245

Asia WGS AF: 0.291 AC: 1013 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.5
DANN	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs7858819; hg19: chr9-4559892;