rs40184

Positions:

• chr5-1394962-C-T

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.1840-204G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 152,138 control chromosomes in the GnomAD database, including 15,566 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.45 (15566 hom., cov: 33)
• Consequence: SLC6A3 NM_001044.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.767

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=-0.98).
• BP6: Variant 5-1394962-C-T is Benign according to our data. Variant chr5-1394962-C-T is described in ClinVar as [Benign]. Clinvar id is 1225506.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A3	NM_001044.5	c.1840-204G>A		intron_variant		ENST00000270349.12	NP_001035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A3	ENST00000270349.12	c.1840-204G>A		intron_variant		1	NM_001044.5	ENSP00000270349	P1
SLC6A3	ENST00000512002.2	n.221-204G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68259 AN: 152020 Hom.: 15553 Cov.: 33

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.449 AC: 68312 AN: 152138 Hom.: 15566 Cov.: 33 AF XY: 0.444 AC XY: 33000 AN XY: 74342

Gnomad4 AFR AF: 0.494

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.481

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.434

Gnomad4 FIN AF: 0.433

Gnomad4 NFE AF: 0.456

Gnomad4 OTH AF: 0.448

Alfa AF: 0.456 Hom.: 23783

Bravo AF: 0.444

Asia WGS AF: 0.380 AC: 1320 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 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.67
DANN	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs40184; hg19: chr5-1395077;