rs2020934

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001045.6(SLC6A4):​c.-221+1171T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 151,968 control chromosomes in the GnomAD database, including 26,052 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 0.57 ( 26052 hom., cov: 32)

Consequence

SLC6A4
NM_001045.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0930
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC6A4NM_001045.6 linkuse as main transcriptc.-221+1171T>C intron_variant ENST00000650711.1 NP_001036.1 P31645-1B2R7Y7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC6A4ENST00000650711.1 linkuse as main transcriptc.-221+1171T>C intron_variant NM_001045.6 ENSP00000498537.1 P31645-1
SLC6A4ENST00000261707.7 linkuse as main transcriptc.-221+1171T>C intron_variant 1 ENSP00000261707.3 P31645-1
SLC6A4ENST00000394821.2 linkuse as main transcriptc.-221+1171T>C intron_variant 1 ENSP00000378298.2 J3KPR9
SLC6A4ENST00000401766.6 linkuse as main transcriptc.-124+1171T>C intron_variant 5 ENSP00000385822.2 P31645-1

Frequencies

GnomAD3 genomes
AF:
0.567
AC:
86119
AN:
151850
Hom.:
25983
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.776
Gnomad AMI
AF:
0.485
Gnomad AMR
AF:
0.454
Gnomad ASJ
AF:
0.401
Gnomad EAS
AF:
0.224
Gnomad SAS
AF:
0.430
Gnomad FIN
AF:
0.560
Gnomad MID
AF:
0.484
Gnomad NFE
AF:
0.514
Gnomad OTH
AF:
0.523
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.568
AC:
86259
AN:
151968
Hom.:
26052
Cov.:
32
AF XY:
0.561
AC XY:
41702
AN XY:
74308
show subpopulations
Gnomad4 AFR
AF:
0.777
Gnomad4 AMR
AF:
0.455
Gnomad4 ASJ
AF:
0.401
Gnomad4 EAS
AF:
0.222
Gnomad4 SAS
AF:
0.430
Gnomad4 FIN
AF:
0.560
Gnomad4 NFE
AF:
0.514
Gnomad4 OTH
AF:
0.527
Alfa
AF:
0.579
Hom.:
3809
Bravo
AF:
0.566
Asia WGS
AF:
0.426
AC:
1479
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.93
CADD
Benign
3.4
DANN
Benign
0.27

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2020934; hg19: chr17-28561460; API