dbSNP rs7212502: SLC6A4:c.-123-103T>C (chr17-30222184-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001045.6(SLC6A4):c.-123-103T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0092 in 700,002 control chromosomes in the GnomAD database, including 314 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 0.030 ( 234 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 80 hom. )

Consequence

SLC6A4
NM_001045.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.733

Publications

3 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A4	NM_001045.6 link	c.-123-103T>C		intron_variant	Intron 2 of 14	ENST00000650711.1	NP_001036.1	P31645-1B2R7Y7

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC6A4	ENST00000650711.1 link	c.-123-103T>C	intron_variant	Intron 2 of 14		NM_001045.6	ENSP00000498537.1	P31645-1
SLC6A4	ENST00000261707.7 link	c.-123-103T>C	intron_variant	Intron 2 of 14	1		ENSP00000261707.3	P31645-1
SLC6A4	ENST00000394821.2 link	c.-123-103T>C	intron_variant	Intron 2 of 14	1		ENSP00000378298.2	J3KPR9
SLC6A4	ENST00000401766.6 link	c.-123-103T>C	intron_variant	Intron 1 of 13	5		ENSP00000385822.2	P31645-1

Frequencies

GnomAD3 genomes

AF:

0.0299

AC:

4545

AN:

152236

Hom.:

233

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00974

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.0215

GnomAD4 exome

AF:

0.00343

AC:

1878

AN:

547648

Hom.:

AF XY:

0.00288

AC XY:

820

AN XY:

285024

show subpopulations

African (AFR)

AF:

0.104

AC:

1494

AN:

14308

American (AMR)

AF:

0.00609

AC:

119

AN:

19528

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13944

East Asian (EAS)

AF:

0.00

AC:

AN:

29432

South Asian (SAS)

AF:

0.000125

AC:

AN:

48008

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32926

Middle Eastern (MID)

AF:

0.00318

AC:

AN:

3142

European-Non Finnish (NFE)

AF:

0.000173

AC:

AN:

357844

Other (OTH)

AF:

0.00656

AC:

187

AN:

28516

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

166

248

331

414

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<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:

152354

Hom.:

234

Cov.:

AF XY:

0.0291

AC XY:

2165

AN XY:

74514

show subpopulations

African (AFR)

AF:

0.105

AC:

4348

AN:

41564

American (AMR)

AF:

0.00973

AC:

149

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.000414

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000279

AC:

AN:

68034

Other (OTH)

AF:

0.0213

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

203

405

608

810

1013

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:

0.0278

Hom.:

Bravo

AF:

0.0340

Asia WGS

AF:

0.00751

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.8

(source)

DANN

Benign

0.49

PhyloP100

0.73

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over