rs2020936

Variant names:

• chr17-30223796-G-A
• rs2020936
• NM_001045.6:c.-220-881C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-30223796-G-A
• chr17-30223796-G-C
• chr17-30223796-G-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.-220-881C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.758 in 151,714 control chromosomes in the GnomAD database, including 44,385 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 0.76 (44385 hom., cov: 28)
• Consequence: SLC6A4 NM_001045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.834
• Publications: 39 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.87 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.-220-881C>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.-220-881C>T		intron	N/A	ENSP00000498537.1	P31645-1
	SLC6A4	ENST00000261707.7	TSL:1	c.-220-881C>T		intron	N/A	ENSP00000261707.3	P31645-1
	SLC6A4	ENST00000394821.2	TSL:1	c.-220-881C>T		intron	N/A	ENSP00000378298.2	J3KPR9

Frequencies

GnomAD3 genomes AF: 0.758 AC: 114963 AN: 151596 Hom.: 44372 Cov.: 28

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.906

Gnomad AMR AF: 0.825

Gnomad ASJ AF: 0.833

Gnomad EAS AF: 0.890

Gnomad SAS AF: 0.824

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.769

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

GnomAD4 genome AF: 0.758 AC: 115017 AN: 151714 Hom.: 44385 Cov.: 28 AF XY: 0.762 AC XY: 56463 AN XY: 74142

African (AFR) AF: 0.592 AC: 24440 AN: 41284

American (AMR) AF: 0.825 AC: 12589 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.833 AC: 2888 AN: 3466

East Asian (EAS) AF: 0.891 AC: 4585 AN: 5144

South Asian (SAS) AF: 0.823 AC: 3958 AN: 4810

European-Finnish (FIN) AF: 0.819 AC: 8611 AN: 10518

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.814 AC: 55259 AN: 67926

Other (OTH) AF: 0.771 AC: 1622 AN: 2104

Alfa AF: 0.795 Hom.: 155260

Bravo AF: 0.753

Asia WGS AF: 0.824 AC: 2863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.37
PhyloP100		-0.83
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: rs2020936; hg19: chr17-28550814;