rs11564752

chr5-1444870-C-Achr5-1444870-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.-46+478G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0661 in 152,344 control chromosomes in the GnomAD database, including 444 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 0.066 (444 hom., cov: 33)
• Consequence: SLC6A3 NM_001044.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.16

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A3	NM_001044.5	c.-46+478G>T		intron_variant		ENST00000270349.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A3	ENST00000270349.12	c.-46+478G>T		intron_variant		1	NM_001044.5	P1

Frequencies

GnomAD3 genomes AF: 0.0661 AC: 10065 AN: 152226 Hom.: 444 Cov.: 33

Gnomad AFR AF: 0.0278

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.0346

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0135

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0963

Gnomad OTH AF: 0.0497

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

GnomAD4 genome AF: 0.0661 AC: 10069 AN: 152344 Hom.: 444 Cov.: 33 AF XY: 0.0654 AC XY: 4874 AN XY: 74490

Gnomad4 AFR AF: 0.0277

Gnomad4 AMR AF: 0.0346

Gnomad4 ASJ AF: 0.0245

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0137

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.0963

Gnomad4 OTH AF: 0.0491

Alfa AF: 0.0402 Hom.: 33

Bravo AF: 0.0582

Asia WGS AF: 0.0120 AC: 42 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.45
Dann	Benign	0.41

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: rs11564752; hg19: chr5-1444985;