rs8076005

Variant names:

• chr17-30220192-G-A
• rs8076005
• NM_001045.6:c.344-1261C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-30220192-G-A
• chr17-30220192-G-C

Variant summary

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

The NM_001045.6(SLC6A4):​c.344-1261C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 152,070 control chromosomes in the GnomAD database, including 39,279 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 0.69 (39279 hom., cov: 32)
• Consequence: SLC6A4 NM_001045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.301
• Publications: 16 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A4	NM_001045.6	c.344-1261C>T		intron_variant	Intron 3 of 14	ENST00000650711.1	NP_001036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A4	ENST00000650711.1	c.344-1261C>T		intron_variant	Intron 3 of 14		NM_001045.6	ENSP00000498537.1
SLC6A4	ENST00000261707.7	c.344-1261C>T		intron_variant	Intron 3 of 14	1		ENSP00000261707.3
SLC6A4	ENST00000394821.2	c.344-1261C>T		intron_variant	Intron 3 of 14	1		ENSP00000378298.2
SLC6A4	ENST00000401766.6	c.344-1261C>T		intron_variant	Intron 2 of 13	5		ENSP00000385822.2

Frequencies

GnomAD3 genomes AF: 0.690 AC: 104814 AN: 151952 Hom.: 39263 Cov.: 32

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.901

Gnomad AMR AF: 0.791

Gnomad ASJ AF: 0.827

Gnomad EAS AF: 0.893

Gnomad SAS AF: 0.822

Gnomad FIN AF: 0.818

Gnomad MID AF: 0.755

Gnomad NFE AF: 0.810

Gnomad OTH AF: 0.715

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

GnomAD4 genome AF: 0.690 AC: 104854 AN: 152070 Hom.: 39279 Cov.: 32 AF XY: 0.695 AC XY: 51681 AN XY: 74338

African (AFR) AF: 0.362 AC: 14980 AN: 41430

American (AMR) AF: 0.791 AC: 12106 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.827 AC: 2872 AN: 3472

East Asian (EAS) AF: 0.894 AC: 4631 AN: 5182

South Asian (SAS) AF: 0.822 AC: 3954 AN: 4812

European-Finnish (FIN) AF: 0.818 AC: 8659 AN: 10582

Middle Eastern (MID) AF: 0.767 AC: 224 AN: 292

European-Non Finnish (NFE) AF: 0.810 AC: 55092 AN: 67980

Other (OTH) AF: 0.717 AC: 1516 AN: 2114

Alfa AF: 0.753 Hom.: 21139

Bravo AF: 0.674

Asia WGS AF: 0.807 AC: 2804 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.7
DANN	Benign	0.48
PhyloP100		0.30
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: rs8076005; hg19: chr17-28547210;