Genetic Variant NM_003054.6:c.-15-39A>C (chr10-117241640-A-C) – 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 NM_003054.6(SLC18A2):c.-15-39A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.991 in 1,504,598 control chromosomes in the GnomAD database, including 739,812 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.95 ( 69485 hom., cov: 33)

Exomes 𝑓: 1.0 ( 670327 hom. )

Consequence

SLC18A2
NM_003054.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.241

Publications

6 publications found

Variant links:

Genes affected

SLC18A2 (HGNC:10935): (solute carrier family 18 member A2) This gene encodes an transmembrane protein that functions as an ATP-dependent transporter of monoamines, such as dopamine, norepinephrine, serotonin, and histamine. This protein transports amine neurotransmitters into synaptic vesicles. Polymorphisms in this gene may be associated with schizophrenia, bipolar disorder, and other neurological/psychiatric ailments. [provided by RefSeq, Jun 2018]

SLC18A2 links:

SLC18A2-AS1 (HGNC:55843): (SLC18A2 antisense RNA 1)

SLC18A2-AS1 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=-0.87).

BP6

Variant 10-117241640-A-C is Benign according to our data. Variant chr10-117241640-A-C is described in ClinVar as Benign. ClinVar VariationId is 1227431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003054.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SLC18A2	NM_003054.6	MANE Select	c.-15-39A>C	intron	N/A	NP_003045.2
SLC18A2-AS1	NR_184309.1		n.113+245T>G	intron	N/A
SLC18A2-AS1	NR_184310.1		n.236+21T>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC18A2	ENST00000644641.2	MANE Select	c.-15-39A>C	intron	N/A	ENSP00000496339.1	Q05940-1
SLC18A2	ENST00000921156.1		c.-54A>C	5_prime_UTR	Exon 1 of 15	ENSP00000591215.1
SLC18A2	ENST00000921159.1		c.-54A>C	5_prime_UTR	Exon 1 of 14	ENSP00000591218.1

Frequencies

GnomAD3 genomes

AF:

0.953

AC:

144885

AN:

151958

Hom.:

69439

Cov.:

show subpopulations

Gnomad AFR

AF:

0.837

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.987

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.978

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.964

GnomAD4 exome

AF:

0.995

AC:

1346087

AN:

1352532

Hom.:

670327

Cov.:

AF XY:

0.996

AC XY:

663890

AN XY:

666624

show subpopulations

African (AFR)

AF:

0.819

AC:

22698

AN:

27722

American (AMR)

AF:

0.991

AC:

31182

AN:

31474

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

23436

AN:

23436

East Asian (EAS)

AF:

1.00

AC:

31100

AN:

31100

South Asian (SAS)

AF:

1.00

AC:

75369

AN:

75400

European-Finnish (FIN)

AF:

1.00

AC:

40009

AN:

40010

Middle Eastern (MID)

AF:

0.991

AC:

3926

AN:

3962

European-Non Finnish (NFE)

AF:

1.00

AC:

1062924

AN:

1063364

Other (OTH)

AF:

0.989

AC:

55443

AN:

56064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

253

506

759

1012

1265

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21098

42196

63294

84392

105490

<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:

0.953

AC:

144984

AN:

152066

Hom.:

69485

Cov.:

AF XY:

0.956

AC XY:

71072

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.837

AC:

34743

AN:

41488

American (AMR)

AF:

0.987

AC:

15103

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3472

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5086

AN:

5086

South Asian (SAS)

AF:

0.999

AC:

4824

AN:

4828

European-Finnish (FIN)

AF:

1.00

AC:

10616

AN:

10616

Middle Eastern (MID)

AF:

0.976

AC:

283

AN:

290

European-Non Finnish (NFE)

AF:

0.999

AC:

67909

AN:

67960

Other (OTH)

AF:

0.964

AC:

2036

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

321

642

962

1283

1604

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

906

1812

2718

3624

4530

<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:

0.942

Hom.:

4925

Bravo

AF:

0.948

Asia WGS

AF:

0.990

AC:

3429

AN:

3462

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Brain dopamine-serotonin vesicular transport disease (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

8.6

(source)

DANN

Benign

0.30

PhyloP100

-0.24

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over