17-30237152-G-A

Variant names:

• chr17-30237152-G-A
• rs25532
• ENST00000855095.1:c.-124+1235C>T

Variant summary

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

The ENST00000855095.1(SLC6A4):​c.-124+1235C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.063 (318 hom., cov: 9)
• Consequence: SLC6A4 ENST00000855095.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85
• Publications: 57 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

ENSG00000266120 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0971 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000855095.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A4	ENST00000855095.1		c.-124+1235C>T		intron	N/A	ENSP00000525154.1
	SLC6A4	ENST00000855096.1		c.-221+1235C>T		intron	N/A	ENSP00000525155.1
	ENSG00000266120	ENST00000724731.1		n.109+82G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0630 AC: 4113 AN: 65304 Hom.: 318 Cov.: 9

Gnomad AFR AF: 0.0136

Gnomad AMI AF: 0.0930

Gnomad AMR AF: 0.0327

Gnomad ASJ AF: 0.0815

Gnomad EAS AF: 0.000842

Gnomad SAS AF: 0.0411

Gnomad FIN AF: 0.0672

Gnomad MID AF: 0.0215

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.0420

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

GnomAD4 genome AF: 0.0629 AC: 4111 AN: 65326 Hom.: 318 Cov.: 9 AF XY: 0.0588 AC XY: 1824 AN XY: 31030

African (AFR) AF: 0.0135 AC: 208 AN: 15356

American (AMR) AF: 0.0326 AC: 256 AN: 7844

Ashkenazi Jewish (ASJ) AF: 0.0815 AC: 148 AN: 1816

East Asian (EAS) AF: 0.000845 AC: 2 AN: 2368

South Asian (SAS) AF: 0.0412 AC: 63 AN: 1530

European-Finnish (FIN) AF: 0.0672 AC: 289 AN: 4302

Middle Eastern (MID) AF: 0.0230 AC: 4 AN: 174

European-Non Finnish (NFE) AF: 0.100 AC: 3067 AN: 30652

Other (OTH) AF: 0.0418 AC: 37 AN: 886

Alfa AF: 0.116 Hom.: 1720

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.55
PhyloP100		-1.8

Splicing

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

Other links and lift over

dbSNP: rs25532; hg19: chr17-28564170;