rs2975292

chr5-1419817-C-Gchr5-1419817-C-T

Variant summary

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

The NM_001044.5(SLC6A3):c.927+752G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 148,102 control chromosomes in the GnomAD database, including 22,099 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 0.53 (22099 hom., cov: 22)
• Consequence: SLC6A3 NM_001044.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90

Genes affected

SLC6A3 (HGNC:11049): (solute carrier family 6 member 3) This gene encodes a dopamine transporter which is a member of the sodium- and chloride-dependent neurotransmitter transporter family. The 3' UTR of this gene contains a 40 bp tandem repeat, referred to as a variable number tandem repeat or VNTR, which can be present in 3 to 11 copies. Variation in the number of repeats is associated with idiopathic epilepsy, attention-deficit hyperactivity disorder, dependence on alcohol and cocaine, susceptibility to Parkinson disease and protection against nicotine dependence.[provided by RefSeq, Nov 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A3	NM_001044.5	c.927+752G>C		intron_variant		ENST00000270349.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A3	ENST00000270349.12	c.927+752G>C		intron_variant		1	NM_001044.5	P1

Frequencies

GnomAD3 genomes AF: 0.529 AC: 78293 AN: 147988 Hom.: 22082 Cov.: 22

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.643

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.529 AC: 78355 AN: 148102 Hom.: 22099 Cov.: 22 AF XY: 0.525 AC XY: 37819 AN XY: 72062

Gnomad4 AFR AF: 0.390

Gnomad4 AMR AF: 0.491

Gnomad4 ASJ AF: 0.545

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.484

Gnomad4 FIN AF: 0.583

Gnomad4 NFE AF: 0.643

Gnomad4 OTH AF: 0.545

Alfa AF: 0.461 Hom.: 1394

Bravo AF: 0.512

Asia WGS AF: 0.356 AC: 1240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.41
Dann	Benign	0.51

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: rs2975292; hg19: chr5-1419932;