rs2455391

Positions:

• chr5-1443383-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001044.5(SLC6A3):​c.-45-141C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 699,060 control chromosomes in the GnomAD database, including 20,455 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3593 hom., cov: 34)
  • Exomes 𝑓: 0.24 (16862 hom.)
• Consequence: SLC6A3 NM_001044.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.777

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 5-1443383-G-A is Benign according to our data. Variant chr5-1443383-G-A is described in ClinVar as [Benign]. Clinvar id is 1265152.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A3	NM_001044.5	c.-45-141C>T		intron_variant		ENST00000270349.12	NP_001035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A3	ENST00000270349.12	c.-45-141C>T		intron_variant		1	NM_001044.5	ENSP00000270349	P1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30375 AN: 152138 Hom.: 3580 Cov.: 34

Gnomad AFR AF: 0.0731

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.209

GnomAD4 exome AF: 0.239 AC: 130891 AN: 546804 Hom.: 16862 AF XY: 0.243 AC XY: 70255 AN XY: 288892

Gnomad4 AFR exome AF: 0.0705

Gnomad4 AMR exome AF: 0.237

Gnomad4 ASJ exome AF: 0.165

Gnomad4 EAS exome AF: 0.131

Gnomad4 SAS exome AF: 0.294

Gnomad4 FIN exome AF: 0.288

Gnomad4 NFE exome AF: 0.249

Gnomad4 OTH exome AF: 0.234

GnomAD4 genome AF: 0.200 AC: 30408 AN: 152256 Hom.: 3593 Cov.: 34 AF XY: 0.202 AC XY: 15047 AN XY: 74436

Gnomad4 AFR AF: 0.0729

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.284

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.258

Gnomad4 OTH AF: 0.215

Alfa AF: 0.220 Hom.: 634

Bravo AF: 0.186

Asia WGS AF: 0.213 AC: 737 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 15, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.26
DANN	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2455391; hg19: chr5-1443498;