chr17-30200210-T-C

Variant names:

• chr17-30200210-T-C
• rs9303628
• NM_001045.6:c.1819-1680A>G

Variant summary

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

The NM_001045.6(SLC6A4):​c.1819-1680A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 152,162 control chromosomes in the GnomAD database, including 24,635 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 0.56 (24635 hom., cov: 33)
• Consequence: SLC6A4 NM_001045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.769
• Publications: 17 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A4	NM_001045.6	c.1819-1680A>G		intron_variant	Intron 14 of 14	ENST00000650711.1	NP_001036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A4	ENST00000650711.1	c.1819-1680A>G		intron_variant	Intron 14 of 14		NM_001045.6	ENSP00000498537.1

Frequencies

GnomAD3 genomes AF: 0.560 AC: 85076 AN: 152044 Hom.: 24609 Cov.: 33

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.817

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.568

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

GnomAD4 genome AF: 0.560 AC: 85141 AN: 152162 Hom.: 24635 Cov.: 33 AF XY: 0.563 AC XY: 41850 AN XY: 74400

African (AFR) AF: 0.672 AC: 27871 AN: 41504

American (AMR) AF: 0.577 AC: 8831 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.584 AC: 2027 AN: 3470

East Asian (EAS) AF: 0.818 AC: 4234 AN: 5174

South Asian (SAS) AF: 0.556 AC: 2683 AN: 4822

European-Finnish (FIN) AF: 0.450 AC: 4764 AN: 10592

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.484 AC: 32934 AN: 67988

Other (OTH) AF: 0.564 AC: 1193 AN: 2116

Alfa AF: 0.517 Hom.: 3195

Bravo AF: 0.577

Asia WGS AF: 0.629 AC: 2188 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.83
DANN	Benign	0.47
PhyloP100		-0.77
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs9303628; hg19: chr17-28527228;