rs2042449

chr5-1416531-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001044.5(SLC6A3):c.928-330C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 453,554 control chromosomes in the GnomAD database, including 11,108 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (3208 hom., cov: 32)
  • Exomes 𝑓: 0.22 (7900 hom.)
• Consequence: SLC6A3 NM_001044.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0360

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 5-1416531-G-A is Benign according to our data. Variant chr5-1416531-G-A is described in ClinVar as [Benign]. Clinvar id is 1247436.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A3	NM_001044.5	c.928-330C>T		intron_variant		ENST00000270349.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A3	ENST00000270349.12	c.928-330C>T		intron_variant		1	NM_001044.5	P1
SLC6A3	ENST00000511750.1	n.48C>T		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30572 AN: 151182 Hom.: 3202 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.205

GnomAD4 exome AF: 0.223 AC: 67423 AN: 302248 Hom.: 7900 Cov.: 0 AF XY: 0.227 AC XY: 36430 AN XY: 160686

Gnomad4 AFR exome AF: 0.140

Gnomad4 AMR exome AF: 0.213

Gnomad4 ASJ exome AF: 0.211

Gnomad4 EAS exome AF: 0.115

Gnomad4 SAS exome AF: 0.272

Gnomad4 FIN exome AF: 0.259

Gnomad4 NFE exome AF: 0.224

Gnomad4 OTH exome AF: 0.225

GnomAD4 genome AF: 0.202 AC: 30605 AN: 151306 Hom.: 3208 Cov.: 32 AF XY: 0.205 AC XY: 15182 AN XY: 73920

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.132

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.264

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.209

Alfa AF: 0.220 Hom.: 4391

Bravo AF: 0.190

Asia WGS AF: 0.228 AC: 791 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.69
Dann	Benign	0.39

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: rs2042449; hg19: chr5-1416646;