rs4532349

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_003664.5(AP3B1):c.1038T>C(p.Asn346Asn) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 1,604,018 control chromosomes in the GnomAD database, including 38,199 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2847 hom., cov: 32)

Exomes 𝑓: 0.21 ( 35352 hom. )

Consequence

AP3B1
NM_003664.5 splice_region, synonymous

Scores

Splicing: ADA: 0.001395

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8O:1

Conservation

PhyloP100: 3.11

Publications

19 publications found

Variant links:

Genes affected

AP3B1 (HGNC:566): (adaptor related protein complex 3 subunit beta 1) This gene encodes a protein that may play a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes. The encoded protein is part of the heterotetrameric AP-3 protein complex which interacts with the scaffolding protein clathrin. Mutations in this gene are associated with Hermansky-Pudlak syndrome type 2. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2012]

AP3B1 Gene-Disease associations (from GenCC):

Hermansky-Pudlak syndrome 2
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, G2P

AP3B1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 5-78177341-A-G is Benign according to our data. Variant chr5-78177341-A-G is described in ClinVar as [Benign]. Clinvar id is 178705.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.11 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AP3B1	NM_003664.5 link	c.1038T>C	p.Asn346Asn	splice_region_variant, synonymous_variant	Exon 9 of 27	ENST00000255194.11	NP_003655.3	O00203-1A0A0S2Z5J4
AP3B1	NM_001271769.2 link	c.891T>C	p.Asn297Asn	splice_region_variant, synonymous_variant	Exon 9 of 27		NP_001258698.1	O00203-3A0A0S2Z5J4
AP3B1	NM_001410752.1 link	c.1038T>C	p.Asn346Asn	splice_region_variant, synonymous_variant	Exon 9 of 23		NP_001397681.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP3B1	ENST00000255194.11 link	c.1038T>C	p.Asn346Asn	splice_region_variant, synonymous_variant	Exon 9 of 27	1	NM_003664.5	ENSP00000255194.7		O00203-1

Frequencies

GnomAD3 genomes

AF:

0.184

AC:

27948

AN:

152022

Hom.:

2843

Cov.:

show subpopulations

Gnomad AFR

AF:

0.115

Gnomad AMI

AF:

0.164

Gnomad AMR

AF:

0.270

Gnomad ASJ

AF:

0.156

Gnomad EAS

AF:

0.0694

Gnomad SAS

AF:

0.124

Gnomad FIN

AF:

0.165

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.224

Gnomad OTH

AF:

0.185

GnomAD2 exomes

AF:

0.194

AC:

48604

AN:

251172

AF XY:

0.188

show subpopulations

Gnomad AFR exome

AF:

0.114

Gnomad AMR exome

AF:

0.298

Gnomad ASJ exome

AF:

0.173

Gnomad EAS exome

AF:

0.0598

Gnomad FIN exome

AF:

0.171

Gnomad NFE exome

AF:

0.220

Gnomad OTH exome

AF:

0.203

GnomAD4 exome

AF:

0.214

AC:

310203

AN:

1451880

Hom.:

35352

Cov.:

AF XY:

0.211

AC XY:

152200

AN XY:

722954

show subpopulations

African (AFR)

AF:

0.103

AC:

3446

AN:

33334

American (AMR)

AF:

0.293

AC:

13076

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.173

AC:

4520

AN:

26058

East Asian (EAS)

AF:

0.0748

AC:

2964

AN:

39612

South Asian (SAS)

AF:

0.120

AC:

10292

AN:

86008

European-Finnish (FIN)

AF:

0.175

AC:

9319

AN:

53386

Middle Eastern (MID)

AF:

0.120

AC:

691

AN:

5748

European-Non Finnish (NFE)

AF:

0.230

AC:

254138

AN:

1102966

Other (OTH)

AF:

0.196

AC:

11757

AN:

60086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

10149

20298

30447

40596

50745

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.184

AC:

27972

AN:

152138

Hom.:

2847

Cov.:

AF XY:

0.182

AC XY:

13499

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.115

AC:

4783

AN:

41516

American (AMR)

AF:

0.271

AC:

4134

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.156

AC:

541

AN:

3466

East Asian (EAS)

AF:

0.0688

AC:

357

AN:

5188

South Asian (SAS)

AF:

0.125

AC:

603

AN:

4824

European-Finnish (FIN)

AF:

0.165

AC:

1743

AN:

10582

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.224

AC:

15232

AN:

67978

Other (OTH)

AF:

0.187

AC:

396

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1130

2261

3391

4522

5652

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.210

Hom.:

5495

Bravo

AF:

0.187

Asia WGS

AF:

0.126

AC:

438

AN:

3478

EpiCase

AF:

0.217

EpiControl

AF:

0.219

ClinVar

Significance: Benign

Submissions summary: Benign:8Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Jun 13, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Benign based on MAF (12-22% in ESP populations) -

Feb 09, 2025

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 44% of patients studied by a panel of primary immunodeficiencies. Number of patients: 42. Only high quality variants are reported. -

not provided

Benign:2Other:1

GenomeConnect, ClinGen

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

Nov 27, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Hermansky-Pudlak syndrome 2

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hermansky-Pudlak syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=48/52

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0014

dbscSNV1_RF

Benign

0.010

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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rs4532349

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over