dbSNP rs2278355: AP3B2:c.2834-151G>A (chr15-82662403-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_001278512.2(AP3B2):c.2834-151G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 685,728 control chromosomes in the GnomAD database, including 113,205 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 0.54 ( 22932 hom., cov: 32)

Exomes 𝑓: 0.58 ( 90273 hom. )

Consequence

AP3B2
NM_001278512.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0890

Publications

7 publications found

Variant links:

Genes affected

AP3B2 (HGNC:567): (adaptor related protein complex 3 subunit beta 2) Adaptor protein complex 3 (AP-3 complex) is a heterotrimeric protein complex involved in the formation of clathrin-coated synaptic vesicles. The protein encoded by this gene represents the beta subunit of the neuron-specific AP-3 complex and was first identified as the target antigen in human paraneoplastic neurologic disorders. The encoded subunit binds clathrin and is phosphorylated by a casein kinase-like protein, which mediates synaptic vesicle coat assembly. Defects in this gene are a cause of early-onset epileptic encephalopathy. [provided by RefSeq, Feb 2017]

AP3B2 links:

CPEB1-AS1 (HGNC:27523): (CPEB1 antisense RNA 1)

CPEB1-AS1 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=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AP3B2	NM_001278512.2 link	c.2834-151G>A		intron_variant	Intron 23 of 26	ENST00000535359.6	NP_001265441.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP3B2	ENST00000535359.6 link	c.2834-151G>A		intron_variant	Intron 23 of 26	1	NM_001278512.2	ENSP00000440984.1		Q13367-4

Frequencies

GnomAD3 genomes

AF:

0.544

AC:

82650

AN:

151828

Hom.:

22908

Cov.:

show subpopulations

Gnomad AFR

AF:

0.426

Gnomad AMI

AF:

0.482

Gnomad AMR

AF:

0.594

Gnomad ASJ

AF:

0.596

Gnomad EAS

AF:

0.513

Gnomad SAS

AF:

0.512

Gnomad FIN

AF:

0.545

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.608

Gnomad OTH

AF:

0.556

GnomAD4 exome

AF:

0.579

AC:

309021

AN:

533782

Hom.:

90273

Cov.:

AF XY:

0.576

AC XY:

160976

AN XY:

279674

show subpopulations

African (AFR)

AF:

0.424

AC:

6058

AN:

14286

American (AMR)

AF:

0.624

AC:

14336

AN:

22964

Ashkenazi Jewish (ASJ)

AF:

0.596

AC:

8916

AN:

14968

East Asian (EAS)

AF:

0.480

AC:

15163

AN:

31600

South Asian (SAS)

AF:

0.505

AC:

24672

AN:

48870

European-Finnish (FIN)

AF:

0.539

AC:

20343

AN:

37754

Middle Eastern (MID)

AF:

0.541

AC:

1209

AN:

2234

European-Non Finnish (NFE)

AF:

0.608

AC:

202000

AN:

332250

Other (OTH)

AF:

0.566

AC:

16324

AN:

28856

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

6929

13857

20786

27714

34643

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1928

3856

5784

7712

9640

<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:

0.544

AC:

82714

AN:

151946

Hom.:

22932

Cov.:

AF XY:

0.542

AC XY:

40246

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.426

AC:

17629

AN:

41426

American (AMR)

AF:

0.594

AC:

9071

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.596

AC:

2069

AN:

3472

East Asian (EAS)

AF:

0.514

AC:

2642

AN:

5140

South Asian (SAS)

AF:

0.513

AC:

2475

AN:

4820

European-Finnish (FIN)

AF:

0.545

AC:

5753

AN:

10548

Middle Eastern (MID)

AF:

0.507

AC:

149

AN:

294

European-Non Finnish (NFE)

AF:

0.608

AC:

41310

AN:

67950

Other (OTH)

AF:

0.557

AC:

1177

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1902

3805

5707

7610

9512

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

716

1432

2148

2864

3580

<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:

0.587

Hom.:

5965

Bravo

AF:

0.549

Asia WGS

AF:

0.543

AC:

1886

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.4

(source)

DANN

Benign

0.59

PhyloP100

0.089

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