Genetic Variant AP3B1:c.*588A>G (chr5-78002314-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBA1

The NM_001271769.2(AP3B1):c.*588A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 297,896 control chromosomes in the GnomAD database, including 130 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.022 ( 112 hom., cov: 33)

Exomes 𝑓: 0.0052 ( 18 hom. )

Consequence

AP3B1
NM_001271769.2 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.698

Publications

1 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:

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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=-0.36).

BP6

Variant 5-78002314-T-C is Benign according to our data. Variant chr5-78002314-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 369508.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AP3B1	NM_001271769.2 link	c.*588A>G		3_prime_UTR_variant	Exon 27 of 27		NP_001258698.1	O00203-3A0A0S2Z5J4
AP3B1	NM_003664.5 link	c.*588A>G		downstream_gene_variant		ENST00000255194.11	NP_003655.3	O00203-1A0A0S2Z5J4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP3B1	ENST00000255194.11 link	c.*588A>G		downstream_gene_variant		1	NM_003664.5	ENSP00000255194.7		O00203-1

Frequencies

GnomAD3 genomes

AF:

0.0223

AC:

3398

AN:

152160

Hom.:

112

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0687

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0232

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00190

Gnomad OTH

AF:

0.0244

GnomAD4 exome

AF:

0.00523

AC:

761

AN:

145618

Hom.:

Cov.:

AF XY:

0.00487

AC XY:

361

AN XY:

74104

show subpopulations

African (AFR)

AF:

0.0584

AC:

293

AN:

5014

American (AMR)

AF:

0.0177

AC:

AN:

4632

Ashkenazi Jewish (ASJ)

AF:

0.00200

AC:

AN:

5994

East Asian (EAS)

AF:

0.00

AC:

AN:

12964

South Asian (SAS)

AF:

0.00

AC:

AN:

1332

European-Finnish (FIN)

AF:

0.000107

AC:

AN:

9304

Middle Eastern (MID)

AF:

0.0267

AC:

AN:

748

European-Non Finnish (NFE)

AF:

0.00230

AC:

220

AN:

95544

Other (OTH)

AF:

0.0132

AC:

133

AN:

10086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

103

137

171

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0224

AC:

3404

AN:

152278

Hom.:

112

Cov.:

AF XY:

0.0212

AC XY:

1581

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0686

AC:

2851

AN:

41544

American (AMR)

AF:

0.0232

AC:

355

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00190

AC:

129

AN:

68022

Other (OTH)

AF:

0.0241

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

175

350

526

701

876

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0194

Hom.:

Bravo

AF:

0.0257

Asia WGS

AF:

0.00607

AC:

AN:

3474

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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

-0.36

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

0.70

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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chr5-78002314-T-C

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