Variant 17-30196708-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.*1748C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 152,166 control chromosomes in the GnomAD database, including 19,309 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 19298 hom., cov: 32)

Exomes 𝑓: 0.36 ( 11 hom. )

Consequence

SLC6A4
NM_001045.6 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.498

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 17-30196708-G-T is Benign according to our data. Variant chr17-30196708-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 322509.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A4	NM_001045.6 link	c.*1748C>A		3_prime_UTR_variant	15/15	ENST00000650711.1	NP_001036.1	P31645-1B2R7Y7

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC6A4	ENST00000650711 link	c.*1748C>A	3_prime_UTR_variant	15/15		NM_001045.6	ENSP00000498537.1	P31645-1
SLC6A4	ENST00000261707 link	c.*1748C>A	3_prime_UTR_variant	15/15	1		ENSP00000261707.3	P31645-1
SLC6A4	ENST00000401766 link	c.*1748C>A	3_prime_UTR_variant	14/14	5		ENSP00000385822.2	P31645-1

Frequencies

GnomAD3 genomes

AF:

0.497

AC:

75454

AN:

151902

Hom.:

19293

Cov.:

show subpopulations

Gnomad AFR

AF:

0.514

Gnomad AMI

AF:

0.468

Gnomad AMR

AF:

0.541

Gnomad ASJ

AF:

0.560

Gnomad EAS

AF:

0.814

Gnomad SAS

AF:

0.534

Gnomad FIN

AF:

0.439

Gnomad MID

AF:

0.525

Gnomad NFE

AF:

0.455

Gnomad OTH

AF:

0.514

GnomAD4 exome

AF:

0.356

AC:

AN:

146

Hom.:

Cov.:

AF XY:

0.354

AC XY:

AN XY:

show subpopulations

Gnomad4 EAS exome

AF:

0.346

Gnomad4 FIN exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.333

Gnomad4 OTH exome

AF:

1.00

GnomAD4 genome

AF:

0.497

AC:

75480

AN:

152020

Hom.:

19298

Cov.:

AF XY:

0.501

AC XY:

37261

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.514

Gnomad4 AMR

AF:

0.541

Gnomad4 ASJ

AF:

0.560

Gnomad4 EAS

AF:

0.815

Gnomad4 SAS

AF:

0.533

Gnomad4 FIN

AF:

0.439

Gnomad4 NFE

AF:

0.455

Gnomad4 OTH

AF:

0.509

Alfa

AF:

0.486

Hom.:

3198

Bravo

AF:

0.508

Asia WGS

AF:

0.607

AC:

2113

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

-0.95

CADD

Benign

0.33

DANN

Benign

0.67

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