rs1049524

Variant names:

• chr5-36687291-G-A
• rs1049524
• NM_004172.5:c.*1022G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-36687291-G-A
• chr5-36687291-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004172.5(SLC1A3):​c.*1022G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 152,136 control chromosomes in the GnomAD database, including 9,463 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (9462 hom., cov: 33)
  • Exomes 𝑓: 0.43 (1 hom.)
• Consequence: SLC1A3 NM_004172.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0870
• Publications: 9 publications found

Genes affected

SLC1A3 (HGNC:10941): (solute carrier family 1 member 3) This gene encodes a member of a member of a high affinity glutamate transporter family. This gene functions in the termination of excitatory neurotransmission in central nervous system. Mutations are associated with episodic ataxia, Type 6. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Feb 2014]

SLC1A3-AS1 (HGNC:56374): (SLC1A3 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 5-36687291-G-A is Benign according to our data. Variant chr5-36687291-G-A is described in ClinVar as Benign. ClinVar VariationId is 353344.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A3	NM_004172.5	c.*1022G>A		3_prime_UTR_variant	Exon 10 of 10	ENST00000265113.9	NP_004163.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A3	ENST00000265113.9	c.*1022G>A		3_prime_UTR_variant	Exon 10 of 10	1	NM_004172.5	ENSP00000265113.4

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48195 AN: 152004 Hom.: 9468 Cov.: 33

Gnomad AFR AF: 0.0819

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.338

GnomAD4 exome AF: 0.429 AC: 6 AN: 14 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 4 AN XY: 8

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 5 AN: 10

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.317 AC: 48181 AN: 152122 Hom.: 9462 Cov.: 33 AF XY: 0.318 AC XY: 23602 AN XY: 74332

African (AFR) AF: 0.0817 AC: 3392 AN: 41522

American (AMR) AF: 0.297 AC: 4545 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1583 AN: 3472

East Asian (EAS) AF: 0.443 AC: 2288 AN: 5166

South Asian (SAS) AF: 0.511 AC: 2464 AN: 4818

European-Finnish (FIN) AF: 0.343 AC: 3627 AN: 10574

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.428 AC: 29070 AN: 67974

Other (OTH) AF: 0.338 AC: 712 AN: 2108

Alfa AF: 0.368 Hom.: 4195

Bravo AF: 0.300

Asia WGS AF: 0.445 AC: 1549 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Episodic ataxia type 6 Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.5
DANN	Benign	0.71
PhyloP100		0.087
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: rs1049524; hg19: chr5-36687393;