rs140701

Variant names:

• chr17-30211514-C-T
• rs140701
• NM_001045.6:c.1205-90G>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.1205-90G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 789,518 control chromosomes in the GnomAD database, including 83,061 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 0.41 (13911 hom., cov: 32)
  • Exomes 𝑓: 0.45 (69150 hom.)
• Consequence: SLC6A4 NM_001045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12
• Publications: 62 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):

• obsessive-compulsive disorder

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia
• 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 = 0.794 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001045.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A4	NM_001045.6	MANE Select	c.1205-90G>A		intron	N/A	NP_001036.1	P31645-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A4	ENST00000650711.1	MANE Select	c.1205-90G>A		intron	N/A	ENSP00000498537.1	P31645-1
	SLC6A4	ENST00000261707.7	TSL:1	c.1205-90G>A		intron	N/A	ENSP00000261707.3	P31645-1
	SLC6A4	ENST00000394821.2	TSL:1	c.1205-90G>A		intron	N/A	ENSP00000378298.2	J3KPR9

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62769 AN: 151934 Hom.: 13914 Cov.: 32

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.814

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.445

GnomAD4 exome AF: 0.454 AC: 289591 AN: 637464 Hom.: 69150 AF XY: 0.455 AC XY: 154850 AN XY: 340354

African (AFR) AF: 0.316 AC: 5746 AN: 18194

American (AMR) AF: 0.549 AC: 19691 AN: 35856

Ashkenazi Jewish (ASJ) AF: 0.536 AC: 10397 AN: 19382

East Asian (EAS) AF: 0.806 AC: 28464 AN: 35332

South Asian (SAS) AF: 0.478 AC: 30557 AN: 63936

European-Finnish (FIN) AF: 0.401 AC: 19943 AN: 49672

Middle Eastern (MID) AF: 0.492 AC: 2019 AN: 4102

European-Non Finnish (NFE) AF: 0.418 AC: 157816 AN: 377808

Other (OTH) AF: 0.451 AC: 14958 AN: 33182

GnomAD4 genome AF: 0.413 AC: 62780 AN: 152054 Hom.: 13911 Cov.: 32 AF XY: 0.422 AC XY: 31325 AN XY: 74308

African (AFR) AF: 0.308 AC: 12753 AN: 41470

American (AMR) AF: 0.501 AC: 7653 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 1881 AN: 3470

East Asian (EAS) AF: 0.815 AC: 4208 AN: 5164

South Asian (SAS) AF: 0.483 AC: 2327 AN: 4816

European-Finnish (FIN) AF: 0.397 AC: 4194 AN: 10554

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.416 AC: 28259 AN: 67982

Other (OTH) AF: 0.442 AC: 930 AN: 2106

Alfa AF: 0.430 Hom.: 18593

Bravo AF: 0.420

Asia WGS AF: 0.566 AC: 1972 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.8
DANN	Benign	0.42
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs140701; hg19: chr17-28538532;