NM_001045.6:c.-220-1732C>T

Variant names:

• chr17-30224647-G-A
• rs2066713
• NM_001045.6:c.-220-1732C>T

Variant summary

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

The NM_001045.6(SLC6A4):​c.-220-1732C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 152,060 control chromosomes in the GnomAD database, including 9,252 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 0.34 (9252 hom., cov: 32)
• Consequence: SLC6A4 NM_001045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.966
• Publications: 64 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.389 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.-220-1732C>T		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.-220-1732C>T		intron	N/A	ENSP00000498537.1	P31645-1
	SLC6A4	ENST00000261707.7	TSL:1	c.-220-1732C>T		intron	N/A	ENSP00000261707.3	P31645-1
	SLC6A4	ENST00000394821.2	TSL:1	c.-220-1732C>T		intron	N/A	ENSP00000378298.2	J3KPR9

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51314 AN: 151942 Hom.: 9236 Cov.: 32

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.0738

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.338 AC: 51358 AN: 152060 Hom.: 9252 Cov.: 32 AF XY: 0.334 AC XY: 24828 AN XY: 74336

African (AFR) AF: 0.265 AC: 10983 AN: 41474

American (AMR) AF: 0.320 AC: 4889 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1040 AN: 3470

East Asian (EAS) AF: 0.0736 AC: 381 AN: 5176

South Asian (SAS) AF: 0.299 AC: 1442 AN: 4820

European-Finnish (FIN) AF: 0.449 AC: 4742 AN: 10566

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.393 AC: 26718 AN: 67956

Other (OTH) AF: 0.317 AC: 670 AN: 2112

Alfa AF: 0.366 Hom.: 44514

Bravo AF: 0.323

Asia WGS AF: 0.235 AC: 817 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.72
DANN	Benign	0.51
PhyloP100		-0.97
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: rs2066713; hg19: chr17-28551665;