17-30216371-C-T

Variant names:

• chr17-30216371-C-T
• rs140700
• NM_001045.6:c.838-155G>A

Variant summary

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

The NM_001045.6(SLC6A4):​c.838-155G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0732 in 151,650 control chromosomes in the GnomAD database, including 403 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 0.073 (403 hom., cov: 30)
• Consequence: SLC6A4 NM_001045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.107
• Publications: 53 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A4	NM_001045.6	c.838-155G>A		intron_variant	Intron 6 of 14	ENST00000650711.1	NP_001036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A4	ENST00000650711.1	c.838-155G>A		intron_variant	Intron 6 of 14		NM_001045.6	ENSP00000498537.1
SLC6A4	ENST00000261707.7	c.838-155G>A		intron_variant	Intron 6 of 14	1		ENSP00000261707.3
SLC6A4	ENST00000394821.2	c.838-155G>A		intron_variant	Intron 6 of 14	1		ENSP00000378298.2
SLC6A4	ENST00000401766.6	c.838-155G>A		intron_variant	Intron 5 of 13	5		ENSP00000385822.2

Frequencies

GnomAD3 genomes AF: 0.0731 AC: 11084 AN: 151532 Hom.: 403 Cov.: 30

Gnomad AFR AF: 0.0483

Gnomad AMI AF: 0.0540

Gnomad AMR AF: 0.0438

Gnomad ASJ AF: 0.0554

Gnomad EAS AF: 0.0618

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0937

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0909

Gnomad OTH AF: 0.0725

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

GnomAD4 genome AF: 0.0732 AC: 11097 AN: 151650 Hom.: 403 Cov.: 30 AF XY: 0.0726 AC XY: 5376 AN XY: 74100

African (AFR) AF: 0.0484 AC: 1997 AN: 41282

American (AMR) AF: 0.0440 AC: 671 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.0554 AC: 192 AN: 3466

East Asian (EAS) AF: 0.0614 AC: 317 AN: 5162

South Asian (SAS) AF: 0.115 AC: 552 AN: 4790

European-Finnish (FIN) AF: 0.0937 AC: 981 AN: 10474

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0909 AC: 6173 AN: 67926

Other (OTH) AF: 0.0722 AC: 152 AN: 2106

Alfa AF: 0.0797 Hom.: 1679

Bravo AF: 0.0671

Asia WGS AF: 0.0930 AC: 325 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.0
DANN	Benign	0.73
PhyloP100		-0.11
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: rs140700; hg19: chr17-28543389;