Variant chr17-30222880-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001045.6(SLC6A4):c.-185C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 1,299,148 control chromosomes in the GnomAD database, including 422,562 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.78 ( 46989 hom., cov: 33)

Exomes 𝑓: 0.81 ( 375573 hom. )

Consequence

SLC6A4
NM_001045.6 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.543

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]

SLC6A4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 17-30222880-G-T is Benign according to our data. Variant chr17-30222880-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 322546.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A4	NM_001045.6 linkuse as main transcript	c.-185C>A		5_prime_UTR_variant	2/15	ENST00000650711.1	NP_001036.1	P31645-1B2R7Y7

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC6A4	ENST00000650711.1 linkuse as main transcript	c.-185C>A	5_prime_UTR_variant	2/15		NM_001045.6	ENSP00000498537.1	P31645-1
SLC6A4	ENST00000261707.7 linkuse as main transcript	c.-185C>A	5_prime_UTR_variant	2/15	1		ENSP00000261707.3	P31645-1
SLC6A4	ENST00000394821.2 linkuse as main transcript	c.-185C>A	5_prime_UTR_variant	2/15	1		ENSP00000378298.2	J3KPR9
SLC6A4	ENST00000401766.6 linkuse as main transcript	c.-123-799C>A	intron_variant		5		ENSP00000385822.2	P31645-1

Frequencies

GnomAD3 genomes

AF:

0.784

AC:

119208

AN:

152102

Hom.:

46974

Cov.:

show subpopulations

Gnomad AFR

AF:

0.685

Gnomad AMI

AF:

0.908

Gnomad AMR

AF:

0.834

Gnomad ASJ

AF:

0.832

Gnomad EAS

AF:

0.886

Gnomad SAS

AF:

0.823

Gnomad FIN

AF:

0.818

Gnomad MID

AF:

0.820

Gnomad NFE

AF:

0.812

Gnomad OTH

AF:

0.784

GnomAD4 exome

AF:

0.809

AC:

927348

AN:

1146928

Hom.:

375573

Cov.:

AF XY:

0.809

AC XY:

455059

AN XY:

562700

show subpopulations

Gnomad4 AFR exome

AF:

0.673

Gnomad4 AMR exome

AF:

0.867

Gnomad4 ASJ exome

AF:

0.829

Gnomad4 EAS exome

AF:

0.877

Gnomad4 SAS exome

AF:

0.815

Gnomad4 FIN exome

AF:

0.835

Gnomad4 NFE exome

AF:

0.808

Gnomad4 OTH exome

AF:

0.802

GnomAD4 genome

AF:

0.784

AC:

119270

AN:

152220

Hom.:

46989

Cov.:

AF XY:

0.786

AC XY:

58512

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.684

Gnomad4 AMR

AF:

0.834

Gnomad4 ASJ

AF:

0.832

Gnomad4 EAS

AF:

0.887

Gnomad4 SAS

AF:

0.822

Gnomad4 FIN

AF:

0.818

Gnomad4 NFE

AF:

0.812

Gnomad4 OTH

AF:

0.785

Alfa

AF:

0.809

Hom.:

62254

Bravo

AF:

0.782

Asia WGS

AF:

0.827

AC:

2874

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Behavior disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.74

DANN

Benign

0.52

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over