rs2020939

Variant names:

• chr17-30223714-G-A
• rs2020939
• NM_001045.6:c.-220-799C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001045.6(SLC6A4):​c.-220-799C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 151,974 control chromosomes in the GnomAD database, including 11,837 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.35 (11837 hom., cov: 31)
• Consequence: SLC6A4 NM_001045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.215
• Publications: 25 publications found

Genes affected

SLC6A4 (HGNC:11050): (solute carrier family 6 member 4) This gene encodes an integral membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. The encoded protein terminates the action of serotonin and recycles it in a sodium-dependent manner. This protein is a target of psychomotor stimulants, such as amphetamines and cocaine, and is a member of the sodium:neurotransmitter symporter family. A repeat length polymorphism in the promoter of this gene has been shown to affect the rate of serotonin uptake. There have been conflicting results in the literature about the possible effect, if any, that this polymorphism may play in behavior and depression. [provided by RefSeq, May 2019]

SLC6A4 Gene-Disease associations (from GenCC):

• obsessive-compulsive disorder

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia
• autism spectrum disorder

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001045.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A4	NM_001045.6	MANE Select	c.-220-799C>T		intron	N/A	NP_001036.1	P31645-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A4	ENST00000650711.1	MANE Select	c.-220-799C>T		intron	N/A	ENSP00000498537.1	P31645-1
	SLC6A4	ENST00000261707.7	TSL:1	c.-220-799C>T		intron	N/A	ENSP00000261707.3	P31645-1
	SLC6A4	ENST00000394821.2	TSL:1	c.-220-799C>T		intron	N/A	ENSP00000378298.2	J3KPR9

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53632 AN: 151856 Hom.: 11842 Cov.: 31

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.796

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.406

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

GnomAD4 genome AF: 0.353 AC: 53617 AN: 151974 Hom.: 11837 Cov.: 31 AF XY: 0.362 AC XY: 26858 AN XY: 74268

African (AFR) AF: 0.104 AC: 4327 AN: 41472

American (AMR) AF: 0.475 AC: 7256 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 1851 AN: 3466

East Asian (EAS) AF: 0.797 AC: 4103 AN: 5148

South Asian (SAS) AF: 0.517 AC: 2487 AN: 4812

European-Finnish (FIN) AF: 0.369 AC: 3902 AN: 10564

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.416 AC: 28286 AN: 67934

Other (OTH) AF: 0.403 AC: 849 AN: 2108

Alfa AF: 0.394 Hom.: 19540

Bravo AF: 0.353

Asia WGS AF: 0.567 AC: 1972 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.8
DANN	Benign	0.45
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2020939; hg19: chr17-28550732;