rs2020933

Variant names:

• chr17-30234737-A-T
• rs2020933
• NM_001045.6:c.-221+876T>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001045.6(SLC6A4):​c.-221+876T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,202 control chromosomes in the GnomAD database, including 2,600 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 0.14 (2600 hom., cov: 32)
• Consequence: SLC6A4 NM_001045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.394
• Publications: 35 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):

• autism spectrum disorder

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A4	NM_001045.6	c.-221+876T>A		intron_variant	Intron 1 of 14	ENST00000650711.1	NP_001036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A4	ENST00000650711.1	c.-221+876T>A		intron_variant	Intron 1 of 14		NM_001045.6	ENSP00000498537.1
SLC6A4	ENST00000261707.7	c.-221+876T>A		intron_variant	Intron 1 of 14	1		ENSP00000261707.3
SLC6A4	ENST00000394821.2	c.-221+876T>A		intron_variant	Intron 1 of 14	1		ENSP00000378298.2
SLC6A4	ENST00000401766.6	c.-124+876T>A		intron_variant	Intron 1 of 13	5		ENSP00000385822.2

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20592 AN: 152084 Hom.: 2587 Cov.: 32

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0786

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.0546

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.0274

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0569

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.136 AC: 20647 AN: 152202 Hom.: 2600 Cov.: 32 AF XY: 0.133 AC XY: 9928 AN XY: 74434

African (AFR) AF: 0.332 AC: 13748 AN: 41464

American (AMR) AF: 0.0785 AC: 1200 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 414 AN: 3472

East Asian (EAS) AF: 0.0538 AC: 279 AN: 5188

South Asian (SAS) AF: 0.112 AC: 539 AN: 4822

European-Finnish (FIN) AF: 0.0274 AC: 291 AN: 10618

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0569 AC: 3870 AN: 68024

Other (OTH) AF: 0.125 AC: 265 AN: 2114

Alfa AF: 0.106 Hom.: 202

Bravo AF: 0.146

Asia WGS AF: 0.115 AC: 400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	16
DANN	Benign	0.78
PhyloP100		0.39
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: rs2020933; hg19: chr17-28561755;