chr5-1400635-G-A

Position:

• chr5-1400635-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.1839+280C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0505 in 152,266 control chromosomes in the GnomAD database, including 247 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.050 (247 hom., cov: 33)
• Consequence: SLC6A3 NM_001044.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.44

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=-0.96).
• BP6: Variant 5-1400635-G-A is Benign according to our data. Variant chr5-1400635-G-A is described in ClinVar as [Benign]. Clinvar id is 1264708.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A3	NM_001044.5	c.1839+280C>T		intron_variant		ENST00000270349.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A3	ENST00000270349.12	c.1839+280C>T		intron_variant		1	NM_001044.5	P1
SLC6A3	ENST00000512002.2	n.220+280C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0505 AC: 7685 AN: 152148 Hom.: 247 Cov.: 33

Gnomad AFR AF: 0.0170

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.0377

Gnomad ASJ AF: 0.0429

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0617

Gnomad FIN AF: 0.0469

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0776

Gnomad OTH AF: 0.0549

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

GnomAD4 genome AF: 0.0505 AC: 7682 AN: 152266 Hom.: 247 Cov.: 33 AF XY: 0.0485 AC XY: 3608 AN XY: 74454

Gnomad4 AFR AF: 0.0170

Gnomad4 AMR AF: 0.0376

Gnomad4 ASJ AF: 0.0429

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0615

Gnomad4 FIN AF: 0.0469

Gnomad4 NFE AF: 0.0776

Gnomad4 OTH AF: 0.0543

Alfa AF: 0.0690 Hom.: 104

Bravo AF: 0.0475

Asia WGS AF: 0.0280 AC: 97 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

Sep 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.071
DANN	Benign	0.46

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: rs28363151; hg19: chr5-1400750;