5-78228244-TA-TAA

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_003664.5(AP3B1):c.280-6dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 1,555,402 control chromosomes in the GnomAD database, including 67,140 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 8529 hom., cov: 0)

Exomes 𝑓: 0.31 ( 58611 hom. )

Consequence

AP3B1
NM_003664.5 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.10

Publications

6 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 -16 ACMG points.

BP6

Variant 5-78228244-T-TA is Benign according to our data. Variant chr5-78228244-T-TA is described in ClinVar as Benign. ClinVar VariationId is 354253.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
AP3B1	NM_003664.5 link	c.280-6dupT	splice_region_variant, intron_variant	Intron 3 of 26	ENST00000255194.11	NP_003655.3
AP3B1	NM_001271769.2 link	c.133-6dupT	splice_region_variant, intron_variant	Intron 3 of 26		NP_001258698.1
AP3B1	NM_001410752.1 link	c.280-6dupT	splice_region_variant, intron_variant	Intron 3 of 22		NP_001397681.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP3B1	ENST00000255194.11 link	c.280-6_280-5insT		splice_region_variant, intron_variant	Intron 3 of 26	1	NM_003664.5	ENSP00000255194.7

Frequencies

GnomAD3 genomes

AF:

0.334

AC:

50595

AN:

151412

Hom.:

8523

Cov.:

show subpopulations

Gnomad AFR

AF:

0.332

Gnomad AMI

AF:

0.434

Gnomad AMR

AF:

0.304

Gnomad ASJ

AF:

0.396

Gnomad EAS

AF:

0.325

Gnomad SAS

AF:

0.282

Gnomad FIN

AF:

0.366

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.337

Gnomad OTH

AF:

0.325

GnomAD2 exomes

AF:

0.309

AC:

69101

AN:

223498

AF XY:

0.311

show subpopulations

Gnomad AFR exome

AF:

0.318

Gnomad AMR exome

AF:

0.254

Gnomad ASJ exome

AF:

0.369

Gnomad EAS exome

AF:

0.310

Gnomad FIN exome

AF:

0.339

Gnomad NFE exome

AF:

0.322

Gnomad OTH exome

AF:

0.310

GnomAD4 exome

AF:

0.308

AC:

432770

AN:

1403874

Hom.:

58611

Cov.:

AF XY:

0.309

AC XY:

215933

AN XY:

699546

show subpopulations

African (AFR)

AF:

0.320

AC:

10189

AN:

31842

American (AMR)

AF:

0.251

AC:

10788

AN:

42988

Ashkenazi Jewish (ASJ)

AF:

0.372

AC:

9276

AN:

24964

East Asian (EAS)

AF:

0.298

AC:

11421

AN:

38286

South Asian (SAS)

AF:

0.272

AC:

22518

AN:

82764

European-Finnish (FIN)

AF:

0.329

AC:

15909

AN:

48420

Middle Eastern (MID)

AF:

0.394

AC:

2202

AN:

5594

European-Non Finnish (NFE)

AF:

0.310

AC:

332164

AN:

1070908

Other (OTH)

AF:

0.315

AC:

18303

AN:

58108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

12595

25191

37786

50382

62977

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11022

22044

33066

44088

55110

<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:

0.334

AC:

50634

AN:

151528

Hom.:

8529

Cov.:

AF XY:

0.332

AC XY:

24602

AN XY:

74018

show subpopulations

African (AFR)

AF:

0.332

AC:

13721

AN:

41270

American (AMR)

AF:

0.303

AC:

4612

AN:

15208

Ashkenazi Jewish (ASJ)

AF:

0.396

AC:

1371

AN:

3462

East Asian (EAS)

AF:

0.326

AC:

1688

AN:

5180

South Asian (SAS)

AF:

0.280

AC:

1340

AN:

4786

European-Finnish (FIN)

AF:

0.366

AC:

3836

AN:

10478

Middle Eastern (MID)

AF:

0.429

AC:

126

AN:

294

European-Non Finnish (NFE)

AF:

0.337

AC:

22866

AN:

67840

Other (OTH)

AF:

0.323

AC:

679

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1679

3358

5037

6716

8395

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

506

1012

1518

2024

2530

<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:

0.250

Hom.:

761

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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 52% of patients studied by a panel of primary immunodeficiencies. Number of patients: 50. Only high quality variants are reported.

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency

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

Hermansky-Pudlak syndrome 2

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:1

Dec 26, 2018

GeneDx

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

PhyloP100

1.1

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over