9-4551482-C-T

Variant names:

• chr9-4551482-C-T
• rs2039216
• NM_004170.6:c.232+6775C>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.232+6775C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.904 in 152,272 control chromosomes in the GnomAD database, including 62,738 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 0.90 (62738 hom., cov: 32)
• Consequence: SLC1A1 NM_004170.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.663
• Publications: 2 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.964 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.232+6775C>T		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.232+6775C>T		intron	N/A	ENSP00000262352.3	P43005
	SLC1A1	ENST00000931882.1		c.232+6775C>T		intron	N/A	ENSP00000601941.1
	SLC1A1	ENST00000954075.1		c.92-9967C>T		intron	N/A	ENSP00000624134.1

Frequencies

GnomAD3 genomes AF: 0.904 AC: 137517 AN: 152154 Hom.: 62707 Cov.: 32

Gnomad AFR AF: 0.769

Gnomad AMI AF: 0.979

Gnomad AMR AF: 0.944

Gnomad ASJ AF: 0.985

Gnomad EAS AF: 0.986

Gnomad SAS AF: 0.988

Gnomad FIN AF: 0.955

Gnomad MID AF: 0.978

Gnomad NFE AF: 0.950

Gnomad OTH AF: 0.921

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

GnomAD4 genome AF: 0.904 AC: 137610 AN: 152272 Hom.: 62738 Cov.: 32 AF XY: 0.907 AC XY: 67549 AN XY: 74456

African (AFR) AF: 0.769 AC: 31922 AN: 41498

American (AMR) AF: 0.944 AC: 14448 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.985 AC: 3421 AN: 3472

East Asian (EAS) AF: 0.986 AC: 5117 AN: 5190

South Asian (SAS) AF: 0.988 AC: 4763 AN: 4822

European-Finnish (FIN) AF: 0.955 AC: 10150 AN: 10624

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.950 AC: 64665 AN: 68040

Other (OTH) AF: 0.918 AC: 1941 AN: 2114

Alfa AF: 0.936 Hom.: 18098

Bravo AF: 0.898

Asia WGS AF: 0.973 AC: 3382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.81
DANN	Benign	0.80
PhyloP100		-0.66
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: rs2039216; hg19: chr9-4551482;