rs4975646

chr5-1433286-G-A

Variant summary

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

The NM_001044.5(SLC6A3):c.419-588C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 151,784 control chromosomes in the GnomAD database, including 5,458 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 0.24 (5458 hom., cov: 32)
• Consequence: SLC6A3 NM_001044.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.153

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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A3	NM_001044.5	c.419-588C>T		intron_variant		ENST00000270349.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A3	ENST00000270349.12	c.419-588C>T		intron_variant		1	NM_001044.5	P1

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35869 AN: 151666 Hom.: 5459 Cov.: 32

Gnomad AFR AF: 0.0685

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.00892

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.236 AC: 35855 AN: 151784 Hom.: 5458 Cov.: 32 AF XY: 0.232 AC XY: 17208 AN XY: 74172

Gnomad4 AFR AF: 0.0683

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.299

Gnomad4 EAS AF: 0.00894

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.350

Gnomad4 OTH AF: 0.257

Alfa AF: 0.316 Hom.: 5088

Bravo AF: 0.225

Asia WGS AF: 0.114 AC: 398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	1.2
Dann	Benign	0.50

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: rs4975646; hg19: chr5-1433401; COSMIC: COSV54366784;