17-30225755-T-C

Variant names:

• chr17-30225755-T-C
• rs8071667
• NM_001045.6:c.-220-2840A>G

Variant summary

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

The ENST00000650711.1(SLC6A4):​c.-220-2840A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.817 in 152,112 control chromosomes in the GnomAD database, including 50,762 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 0.82 (50762 hom., cov: 31)
• Consequence: SLC6A4 ENST00000650711.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0470
• Publications: 11 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000650711.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A4	NM_001045.6	MANE Select	c.-220-2840A>G		intron	N/A	NP_001036.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A4	ENST00000650711.1	MANE Select	c.-220-2840A>G		intron	N/A	ENSP00000498537.1
	SLC6A4	ENST00000261707.7	TSL:1	c.-220-2840A>G		intron	N/A	ENSP00000261707.3
	SLC6A4	ENST00000394821.2	TSL:1	c.-220-2840A>G		intron	N/A	ENSP00000378298.2

Frequencies

GnomAD3 genomes AF: 0.817 AC: 124167 AN: 151994 Hom.: 50744 Cov.: 31

Gnomad AFR AF: 0.775

Gnomad AMI AF: 0.906

Gnomad AMR AF: 0.848

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 0.901

Gnomad SAS AF: 0.831

Gnomad FIN AF: 0.845

Gnomad MID AF: 0.841

Gnomad NFE AF: 0.821

Gnomad OTH AF: 0.810

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

GnomAD4 genome AF: 0.817 AC: 124239 AN: 152112 Hom.: 50762 Cov.: 31 AF XY: 0.819 AC XY: 60904 AN XY: 74354

African (AFR) AF: 0.774 AC: 32112 AN: 41466

American (AMR) AF: 0.848 AC: 12964 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.844 AC: 2927 AN: 3468

East Asian (EAS) AF: 0.902 AC: 4660 AN: 5168

South Asian (SAS) AF: 0.830 AC: 3991 AN: 4810

European-Finnish (FIN) AF: 0.845 AC: 8952 AN: 10600

Middle Eastern (MID) AF: 0.849 AC: 248 AN: 292

European-Non Finnish (NFE) AF: 0.821 AC: 55843 AN: 68000

Other (OTH) AF: 0.811 AC: 1716 AN: 2116

Alfa AF: 0.818 Hom.: 25311

Bravo AF: 0.816

Asia WGS AF: 0.839 AC: 2916 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.7
DANN	Benign	0.57
PhyloP100		0.047
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: rs8071667; hg19: chr17-28552773;