chr5-1400816-A-ATCTACACCAGCCCTG

Position:

• chr5-1400816-A-ATCTACACCAGCCCTG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001044.5(SLC6A3):​c.1839+98_1839+99insCAGGGCTGGTGTAGA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0842 in 878,280 control chromosomes in the GnomAD database, including 6,878 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (3819 hom., cov: 31)
  • Exomes 𝑓: 0.067 (3059 hom.)
• Consequence: SLC6A3 NM_001044.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.123

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 -10 ACMG points.

• BP6: Variant 5-1400816-A-ATCTACACCAGCCCTG is Benign according to our data. Variant chr5-1400816-A-ATCTACACCAGCCCTG is described in ClinVar as [Benign]. Clinvar id is 1291957.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A3	NM_001044.5	c.1839+98_1839+99insCAGGGCTGGTGTAGA		intron_variant		ENST00000270349.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A3	ENST00000270349.12	c.1839+98_1839+99insCAGGGCTGGTGTAGA		intron_variant		1	NM_001044.5	P1
SLC6A3	ENST00000512002.2	n.220+98_220+99insCAGGGCTGGTGTAGA		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24893 AN: 151866 Hom.: 3800 Cov.: 31

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.0777

Gnomad ASJ AF: 0.0965

Gnomad EAS AF: 0.0218

Gnomad SAS AF: 0.0825

Gnomad FIN AF: 0.0789

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0683

Gnomad OTH AF: 0.122

GnomAD4 exome AF: 0.0675 AC: 49002 AN: 726298 Hom.: 3059 AF XY: 0.0674 AC XY: 25733 AN XY: 381768

Gnomad4 AFR exome AF: 0.394

Gnomad4 AMR exome AF: 0.0507

Gnomad4 ASJ exome AF: 0.0887

Gnomad4 EAS exome AF: 0.0249

Gnomad4 SAS exome AF: 0.0769

Gnomad4 FIN exome AF: 0.0762

Gnomad4 NFE exome AF: 0.0553

Gnomad4 OTH exome AF: 0.0809

GnomAD4 genome AF: 0.164 AC: 24962 AN: 151982 Hom.: 3819 Cov.: 31 AF XY: 0.159 AC XY: 11826 AN XY: 74298

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.0775

Gnomad4 ASJ AF: 0.0965

Gnomad4 EAS AF: 0.0219

Gnomad4 SAS AF: 0.0832

Gnomad4 FIN AF: 0.0789

Gnomad4 NFE AF: 0.0683

Gnomad4 OTH AF: 0.121

Alfa AF: 0.133 Hom.: 232

Asia WGS AF: 0.0800 AC: 280 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

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs28363149; hg19: chr5-1400931;