chr5-78116244-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003664.5(AP3B1):c.1969-10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0692 in 1,593,932 control chromosomes in the GnomAD database, including 4,256 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.053 ( 326 hom., cov: 32)

Exomes 𝑓: 0.071 ( 3930 hom. )

Consequence

AP3B1
NM_003664.5 intron

Scores

Splicing: ADA: 0.0003659

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.179

Publications

3 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 5-78116244-C-T is Benign according to our data. Variant chr5-78116244-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 178702.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
AP3B1	NM_003664.5 link	c.1969-10G>A	intron_variant	Intron 17 of 26	ENST00000255194.11	NP_003655.3	O00203-1A0A0S2Z5J4
AP3B1	NM_001271769.2 link	c.1822-10G>A	intron_variant	Intron 17 of 26		NP_001258698.1	O00203-3A0A0S2Z5J4
AP3B1	NM_001410752.1 link	c.1969-10G>A	intron_variant	Intron 17 of 22		NP_001397681.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP3B1	ENST00000255194.11 link	c.1969-10G>A		intron_variant	Intron 17 of 26	1	NM_003664.5	ENSP00000255194.7		O00203-1

Frequencies

GnomAD3 genomes

AF:

0.0531

AC:

8077

AN:

152090

Hom.:

327

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0129

Gnomad AMI

AF:

0.0329

Gnomad AMR

AF:

0.0530

Gnomad ASJ

AF:

0.0793

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0538

Gnomad FIN

AF:

0.0688

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0777

Gnomad OTH

AF:

0.0660

GnomAD2 exomes

AF:

0.0594

AC:

14856

AN:

250254

AF XY:

0.0619

show subpopulations

Gnomad AFR exome

AF:

0.0108

Gnomad AMR exome

AF:

0.0374

Gnomad ASJ exome

AF:

0.0893

Gnomad EAS exome

AF:

0.000272

Gnomad FIN exome

AF:

0.0690

Gnomad NFE exome

AF:

0.0785

Gnomad OTH exome

AF:

0.0719

GnomAD4 exome

AF:

0.0709

AC:

102280

AN:

1441724

Hom.:

3930

Cov.:

AF XY:

0.0711

AC XY:

51103

AN XY:

718722

show subpopulations

African (AFR)

AF:

0.0118

AC:

391

AN:

33044

American (AMR)

AF:

0.0405

AC:

1810

AN:

44674

Ashkenazi Jewish (ASJ)

AF:

0.0893

AC:

2324

AN:

26036

East Asian (EAS)

AF:

0.000202

AC:

AN:

39526

South Asian (SAS)

AF:

0.0560

AC:

4811

AN:

85900

European-Finnish (FIN)

AF:

0.0701

AC:

3714

AN:

52996

Middle Eastern (MID)

AF:

0.0500

AC:

287

AN:

5740

European-Non Finnish (NFE)

AF:

0.0777

AC:

85001

AN:

1094098

Other (OTH)

AF:

0.0659

AC:

3934

AN:

59710

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

4147

8294

12440

16587

20734

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0530

AC:

8073

AN:

152208

Hom.:

326

Cov.:

AF XY:

0.0529

AC XY:

3935

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.0129

AC:

535

AN:

41546

American (AMR)

AF:

0.0529

AC:

809

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0793

AC:

275

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5188

South Asian (SAS)

AF:

0.0541

AC:

261

AN:

4826

European-Finnish (FIN)

AF:

0.0688

AC:

728

AN:

10580

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0777

AC:

5280

AN:

67994

Other (OTH)

AF:

0.0648

AC:

137

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

386

772

1158

1544

1930

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0639

Hom.:

132

Bravo

AF:

0.0514

Asia WGS

AF:

0.0230

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

1969-10G>A in intron 17 of AP3B1: This variant is not expected to have clinical significance because it has been identified in 7.5% (642/8600) of European Ameri can chromosomes from a broad population by the NHLBI Exome Sequencing Project (h ttp://evs.gs.washington.edu/EVS; dbSNP rs77009095). -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely 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:Likely 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

-0.61

CADD

Benign

(source)

DANN

Benign

0.67

PhyloP100

0.18

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00037

dbscSNV1_RF

Benign

0.15

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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chr5-78116244-C-T

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