Genetic Variant NM_003053.4:c.548-148A>G (chr8-20174592-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_003053.4(SLC18A1):c.548-148A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 608,898 control chromosomes in the GnomAD database, including 7,683 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 0.14 ( 1709 hom., cov: 32)

Exomes 𝑓: 0.15 ( 5974 hom. )

Consequence

SLC18A1
NM_003053.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.104

Publications

3 publications found

Variant links:

Genes affected

SLC18A1 (HGNC:10934): (solute carrier family 18 member A1) The vesicular monoamine transporter acts to accumulate cytosolic monoamines into vesicles, using the proton gradient maintained across the vesicular membrane. Its proper function is essential to the correct activity of the monoaminergic systems that have been implicated in several human neuropsychiatric disorders. The transporter is a site of action of important drugs, including reserpine and tetrabenazine (Peter et al., 1993 [PubMed 7905859]). See also SLC18A2 (MIM 193001).[supplied by OMIM, Mar 2008]

SLC18A1 links:

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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 (NFE) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC18A1	NM_003053.4 link	c.548-148A>G		intron_variant	Intron 4 of 15	ENST00000276373.10	NP_003044.1	P54219-1Q96GL6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC18A1	ENST00000276373.10 link	c.548-148A>G		intron_variant	Intron 4 of 15	1	NM_003053.4	ENSP00000276373.5		P54219-1

Frequencies

GnomAD3 genomes

AF:

0.143

AC:

21745

AN:

151984

Hom.:

1709

Cov.:

show subpopulations

Gnomad AFR

AF:

0.101

Gnomad AMI

AF:

0.198

Gnomad AMR

AF:

0.146

Gnomad ASJ

AF:

0.235

Gnomad EAS

AF:

0.118

Gnomad SAS

AF:

0.0876

Gnomad FIN

AF:

0.0917

Gnomad MID

AF:

0.296

Gnomad NFE

AF:

0.175

Gnomad OTH

AF:

0.171

GnomAD4 exome

AF:

0.151

AC:

68969

AN:

456796

Hom.:

5974

AF XY:

0.149

AC XY:

36072

AN XY:

241988

show subpopulations

African (AFR)

AF:

0.0982

AC:

1242

AN:

12646

American (AMR)

AF:

0.125

AC:

2803

AN:

22450

Ashkenazi Jewish (ASJ)

AF:

0.224

AC:

3182

AN:

14194

East Asian (EAS)

AF:

0.109

AC:

3283

AN:

30042

South Asian (SAS)

AF:

0.0806

AC:

3823

AN:

47454

European-Finnish (FIN)

AF:

0.0916

AC:

3077

AN:

33582

Middle Eastern (MID)

AF:

0.183

AC:

394

AN:

2158

European-Non Finnish (NFE)

AF:

0.175

AC:

46948

AN:

268548

Other (OTH)

AF:

0.164

AC:

4217

AN:

25722

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

2643

5286

7929

10572

13215

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

272

544

816

1088

1360

<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:

0.143

AC:

21750

AN:

152102

Hom.:

1709

Cov.:

AF XY:

0.138

AC XY:

10264

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.101

AC:

4203

AN:

41470

American (AMR)

AF:

0.145

AC:

2222

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.235

AC:

815

AN:

3470

East Asian (EAS)

AF:

0.118

AC:

610

AN:

5162

South Asian (SAS)

AF:

0.0872

AC:

421

AN:

4826

European-Finnish (FIN)

AF:

0.0917

AC:

971

AN:

10586

Middle Eastern (MID)

AF:

0.298

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.175

AC:

11877

AN:

68000

Other (OTH)

AF:

0.173

AC:

364

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

938

1875

2813

3750

4688

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

236

472

708

944

1180

<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:

0.169

Hom.:

9143

Bravo

AF:

0.148

Asia WGS

AF:

0.108

AC:

374

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

2.6

(source)

DANN

Benign

0.64

PhyloP100

-0.10

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