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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004172.5. 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
	SLC1A3	NM_004172.5	MANE Select	c.*1022G>A		3_prime_UTR	Exon 10 of 10	NP_004163.3
	SLC1A3	NM_001438458.1		c.*1022G>A		3_prime_UTR	Exon 11 of 11	NP_001425387.1
	SLC1A3	NM_001438454.1		c.*1022G>A		3_prime_UTR	Exon 11 of 11	NP_001425383.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A3	ENST00000265113.9	TSL:1 MANE Select	c.*1022G>A		3_prime_UTR	Exon 10 of 10	ENSP00000265113.4	P43003-1
	SLC1A3	ENST00000381918.4	TSL:1	c.*1022G>A		3_prime_UTR	Exon 10 of 10	ENSP00000371343.4	P43003-1
	SLC1A3	ENST00000680232.1		c.*1022G>A		3_prime_UTR	Exon 11 of 11	ENSP00000506207.1	A0A7P0TAG7

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Episodic ataxia type 6 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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;