rs2066713

chr17-30224647-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A4	NM_001045.6	c.-220-1732C>T		intron_variant		ENST00000650711.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A4	ENST00000650711.1	c.-220-1732C>T		intron_variant			NM_001045.6	P1
SLC6A4	ENST00000261707.7	c.-220-1732C>T		intron_variant		1		P1
SLC6A4	ENST00000394821.2	c.-220-1732C>T		intron_variant		1
SLC6A4	ENST00000401766.6	c.-123-2566C>T		intron_variant		5		P1

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

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.320

Gnomad4 ASJ AF: 0.300

Gnomad4 EAS AF: 0.0736

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.449

Gnomad4 NFE AF: 0.393

Gnomad4 OTH AF: 0.317

Alfa AF: 0.370 Hom.: 21597

Bravo AF: 0.323

Asia WGS AF: 0.235 AC: 817 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.72
Dann	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs2066713; hg19: chr17-28551665;