chr17-30199457-T-C

Variant names:

• chr17-30199457-T-C
• rs4325622
• NM_001045.6:c.1819-927A>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.1819-927A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 152,062 control chromosomes in the GnomAD database, including 13,526 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 0.38 (13526 hom., cov: 31)
• Consequence: SLC6A4 NM_001045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.591
• Publications: 25 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=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A4	NM_001045.6	c.1819-927A>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.1819-927A>G		intron_variant	Intron 14 of 14		NM_001045.6	ENSP00000498537.1

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57947 AN: 151944 Hom.: 13531 Cov.: 31

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.816

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.426

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

GnomAD4 genome AF: 0.381 AC: 57927 AN: 152062 Hom.: 13526 Cov.: 31 AF XY: 0.390 AC XY: 29012 AN XY: 74326

African (AFR) AF: 0.120 AC: 4979 AN: 41520

American (AMR) AF: 0.495 AC: 7567 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 1902 AN: 3472

East Asian (EAS) AF: 0.817 AC: 4235 AN: 5186

South Asian (SAS) AF: 0.532 AC: 2561 AN: 4818

European-Finnish (FIN) AF: 0.438 AC: 4620 AN: 10548

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.451 AC: 30615 AN: 67928

Other (OTH) AF: 0.423 AC: 890 AN: 2106

Alfa AF: 0.392 Hom.: 1665

Bravo AF: 0.378

Asia WGS AF: 0.576 AC: 2004 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	7.3
DANN	Benign	0.88
PhyloP100		0.59
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: rs4325622; hg19: chr17-28526475;