Genetic Variant NM_001045.6:c.-220-4135G>A (chr17-30227050-C-T) – 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.-220-4135G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0829 in 152,224 control chromosomes in the GnomAD database, including 1,710 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 0.083 ( 1710 hom., cov: 32)

Consequence

SLC6A4
NM_001045.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0740

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=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A4	NM_001045.6 link	c.-220-4135G>A		intron_variant	Intron 1 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.-220-4135G>A	intron_variant	Intron 1 of 14		NM_001045.6	ENSP00000498537.1	P31645-1
SLC6A4	ENST00000261707.7 link	c.-220-4135G>A	intron_variant	Intron 1 of 14	1		ENSP00000261707.3	P31645-1
SLC6A4	ENST00000394821.2 link	c.-220-4135G>A	intron_variant	Intron 1 of 14	1		ENSP00000378298.2	J3KPR9
SLC6A4	ENST00000401766.6 link	c.-123-4969G>A	intron_variant	Intron 1 of 13	5		ENSP00000385822.2	P31645-1

Frequencies

GnomAD3 genomes

AF:

0.0829

AC:

12605

AN:

152106

Hom.:

1705

Cov.:

show subpopulations

Gnomad AFR

AF:

0.287

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0334

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.00143

Gnomad OTH

AF:

0.0535

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0829

AC:

12621

AN:

152224

Hom.:

1710

Cov.:

AF XY:

0.0803

AC XY:

5974

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.286

AC:

11884

AN:

41486

American (AMR)

AF:

0.0333

AC:

510

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00166

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00143

AC:

AN:

68016

Other (OTH)

AF:

0.0530

AC:

112

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

474

948

1421

1895

2369

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

220

330

440

550

<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:

0.167

Hom.:

670

Bravo

AF:

0.0947

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.7

(source)

DANN

Benign

0.75

PhyloP100

0.074

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over