17-30222844-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001045.6(SLC6A4):c.-149C>A variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00593 in 1,304,444 control chromosomes in the GnomAD database, including 391 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.030 ( 233 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 158 hom. )

Consequence

SLC6A4
NM_001045.6 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.88

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

autism spectrum disorder
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

SLC6A4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 17-30222844-G-T is Benign according to our data. Variant chr17-30222844-G-T is described in ClinVar as Benign. ClinVar VariationId is 322543.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A4	NM_001045.6	MANE Select	c.-149C>A		5_prime_UTR_premature_start_codon_gain	Exon 2 of 15	NP_001036.1
	SLC6A4	NM_001045.6	MANE Select	c.-149C>A		5_prime_UTR	Exon 2 of 15	NP_001036.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SLC6A4	ENST00000650711.1	MANE Select	c.-149C>A	5_prime_UTR_premature_start_codon_gain	Exon 2 of 15	ENSP00000498537.1
SLC6A4	ENST00000261707.7	TSL:1	c.-149C>A	5_prime_UTR_premature_start_codon_gain	Exon 2 of 15	ENSP00000261707.3
SLC6A4	ENST00000394821.2	TSL:1	c.-149C>A	5_prime_UTR_premature_start_codon_gain	Exon 2 of 15	ENSP00000378298.2

Frequencies

GnomAD3 genomes

AF:

0.0299

AC:

4545

AN:

152216

Hom.:

232

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0102

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000413

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.0215

GnomAD2 exomes

AF:

0.00559

AC:

851

AN:

152334

AF XY:

0.00442

show subpopulations

Gnomad AFR exome

AF:

0.101

Gnomad AMR exome

AF:

0.00476

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000484

Gnomad OTH exome

AF:

0.00230

GnomAD4 exome

AF:

0.00275

AC:

3167

AN:

1152110

Hom.:

158

Cov.:

AF XY:

0.00228

AC XY:

1288

AN XY:

564932

show subpopulations

African (AFR)

AF:

0.109

AC:

2656

AN:

24390

American (AMR)

AF:

0.00478

AC:

135

AN:

28270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15942

East Asian (EAS)

AF:

0.00

AC:

AN:

12982

South Asian (SAS)

AF:

0.000197

AC:

AN:

76202

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27476

Middle Eastern (MID)

AF:

0.00431

AC:

AN:

4404

European-Non Finnish (NFE)

AF:

0.000148

AC:

136

AN:

920826

Other (OTH)

AF:

0.00495

AC:

206

AN:

41618

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

144

288

431

575

719

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

208

312

416

520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0300

AC:

4564

AN:

152334

Hom.:

233

Cov.:

AF XY:

0.0291

AC XY:

2165

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.104

AC:

4341

AN:

41568

American (AMR)

AF:

0.0102

AC:

156

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000414

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000279

AC:

AN:

68038

Other (OTH)

AF:

0.0213

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

206

412

617

823

1029

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0108

Hom.:

Bravo

AF:

0.0341

Asia WGS

AF:

0.00751

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Behavior disorder

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.75

PhyloP100

3.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over