ENST00000855095.1:c.-124+1059A>G

Variant names:

• chr17-30237328-T-C
• rs25531
• ENST00000855095.1:c.-124+1059A>G

Variant summary

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

The ENST00000855095.1(SLC6A4):​c.-124+1059A>G 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 0.19 (468 hom., cov: 4)
• Consequence: SLC6A4 ENST00000855095.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.732
• Publications: 749 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

ENSG00000266120 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.284 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+1059A>G		intron	N/A	ENSP00000525154.1
	SLC6A4	ENST00000855096.1		c.-221+1059A>G		intron	N/A	ENSP00000525155.1
	ENSG00000266120	ENST00000724731.1		n.109+258T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.187 AC: 5881 AN: 31434 Hom.: 464 Cov.: 4

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.0853

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.0938

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.187 AC: 5896 AN: 31456 Hom.: 468 Cov.: 4 AF XY: 0.196 AC XY: 2750 AN XY: 13996

African (AFR) AF: 0.293 AC: 2651 AN: 9038

American (AMR) AF: 0.179 AC: 344 AN: 1918

Ashkenazi Jewish (ASJ) AF: 0.0853 AC: 72 AN: 844

East Asian (EAS) AF: 0.321 AC: 193 AN: 602

South Asian (SAS) AF: 0.292 AC: 158 AN: 542

European-Finnish (FIN) AF: 0.192 AC: 215 AN: 1120

Middle Eastern (MID) AF: 0.100 AC: 3 AN: 30

European-Non Finnish (NFE) AF: 0.129 AC: 2161 AN: 16750

Other (OTH) AF: 0.186 AC: 75 AN: 404

Alfa AF: 0.0264 Hom.: 20

Bravo AF: 0.119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	5.5
DANN	Benign	0.41
PhyloP100		-0.73

Splicing

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

Other links and lift over

dbSNP: rs25531; hg19: chr17-28564346;