17-30211697-A-G

Variant names:

• chr17-30211697-A-G
• rs4583306
• NM_001045.6:c.1205-273T>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.1205-273T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 152,036 control chromosomes in the GnomAD database, including 12,492 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 (12492 hom., cov: 31)
• Consequence: SLC6A4 NM_001045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.995
• Publications: 26 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A4	NM_001045.6	c.1205-273T>C		intron_variant	Intron 9 of 14	ENST00000650711.1	NP_001036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A4	ENST00000650711.1	c.1205-273T>C		intron_variant	Intron 9 of 14		NM_001045.6	ENSP00000498537.1
SLC6A4	ENST00000261707.7	c.1205-273T>C		intron_variant	Intron 9 of 14	1		ENSP00000261707.3
SLC6A4	ENST00000394821.2	c.1205-273T>C		intron_variant	Intron 9 of 14	1		ENSP00000378298.2
SLC6A4	ENST00000401766.6	c.1205-273T>C		intron_variant	Intron 8 of 13	5		ENSP00000385822.2

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57477 AN: 151918 Hom.: 12495 Cov.: 31

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.817

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.423

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

GnomAD4 genome AF: 0.378 AC: 57472 AN: 152036 Hom.: 12492 Cov.: 31 AF XY: 0.386 AC XY: 28708 AN XY: 74294

African (AFR) AF: 0.193 AC: 7991 AN: 41492

American (AMR) AF: 0.486 AC: 7423 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 1866 AN: 3466

East Asian (EAS) AF: 0.818 AC: 4227 AN: 5168

South Asian (SAS) AF: 0.492 AC: 2370 AN: 4814

European-Finnish (FIN) AF: 0.385 AC: 4068 AN: 10558

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.413 AC: 28078 AN: 67956

Other (OTH) AF: 0.420 AC: 885 AN: 2108

Alfa AF: 0.418 Hom.: 7902

Bravo AF: 0.382

Asia WGS AF: 0.565 AC: 1964 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.9
DANN	Benign	0.65
PhyloP100		0.99
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: rs4583306; hg19: chr17-28538715;