dbSNP rs25533: SLC6A4:c.-482T>C (chr17-30235874-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000261707.7(SLC6A4):c.-482T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0754 in 152,376 control chromosomes in the GnomAD database, including 450 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.075 ( 450 hom., cov: 32)

Exomes 𝑓: 0.077 ( 0 hom. )

Consequence

SLC6A4
ENST00000261707.7 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.85

Publications

18 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 -20 ACMG points.

BP4

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

BP6

Variant 17-30235874-A-G is Benign according to our data. Variant chr17-30235874-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 322550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A4	NM_001045.6 link	c.-482T>C		upstream_gene_variant		ENST00000650711.1	NP_001036.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
SLC6A4	ENST00000261707.7 link	c.-482T>C	5_prime_UTR_variant	Exon 1 of 15	1		ENSP00000261707.3
SLC6A4	ENST00000401766.6 link	c.-385T>C	5_prime_UTR_variant	Exon 1 of 14	5		ENSP00000385822.2
SLC6A4	ENST00000650711.1 link	c.-482T>C	upstream_gene_variant			NM_001045.6	ENSP00000498537.1
SLC6A4	ENST00000394821.2 link	c.-482T>C	upstream_gene_variant		1		ENSP00000378298.2

Frequencies

GnomAD3 genomes

AF:

0.0754

AC:

11467

AN:

152090

Hom.:

451

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0928

Gnomad AMI

AF:

0.0636

Gnomad AMR

AF:

0.0416

Gnomad ASJ

AF:

0.0300

Gnomad EAS

AF:

0.122

Gnomad SAS

AF:

0.0684

Gnomad FIN

AF:

0.0825

Gnomad MID

AF:

0.0605

Gnomad NFE

AF:

0.0712

Gnomad OTH

AF:

0.0606

GnomAD4 exome

AF:

0.0774

AC:

AN:

168

Hom.:

Cov.:

AF XY:

0.0814

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.125

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.0556

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0849

AC:

AN:

106

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0754

AC:

11470

AN:

152208

Hom.:

450

Cov.:

AF XY:

0.0745

AC XY:

5548

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.0926

AC:

3846

AN:

41530

American (AMR)

AF:

0.0415

AC:

636

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0300

AC:

104

AN:

3470

East Asian (EAS)

AF:

0.122

AC:

627

AN:

5156

South Asian (SAS)

AF:

0.0693

AC:

334

AN:

4822

European-Finnish (FIN)

AF:

0.0825

AC:

876

AN:

10614

Middle Eastern (MID)

AF:

0.0582

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0712

AC:

4842

AN:

67988

Other (OTH)

AF:

0.0614

AC:

130

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

572

1144

1717

2289

2861

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

264

396

528

660

<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:

0.193

Hom.:

1409

Bravo

AF:

0.0714

Asia WGS

AF:

0.114

AC:

397

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

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.6

(source)

DANN

Benign

0.39

PhyloP100

-1.9

PromoterAI

0.063

Neutral

(source)

Mutation Taster

=300/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over