Variant rs112329411 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003664.5(AP3B1):c.1364-18A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00302 in 1,503,960 control chromosomes in the GnomAD database, including 127 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.015 ( 68 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 59 hom. )

Consequence

AP3B1
NM_003664.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.311

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 5-78156385-T-C is Benign according to our data. Variant chr5-78156385-T-C is described in ClinVar as [Benign]. Clinvar id is 259118.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
AP3B1	NM_003664.5 linkuse as main transcript	c.1364-18A>G	intron_variant	ENST00000255194.11
AP3B1	NM_001271769.2 linkuse as main transcript	c.1217-18A>G	intron_variant
AP3B1	NM_001410752.1 linkuse as main transcript	c.1364-18A>G	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AP3B1	ENST00000255194.11 linkuse as main transcript	c.1364-18A>G		intron_variant		1	NM_003664.5	P2	O00203-1

Frequencies

GnomAD3 genomes

AF:

0.0151

AC:

2299

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0528

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00425

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.00411

AC:

1027

AN:

249814

Hom.:

AF XY:

0.00303

AC XY:

410

AN XY:

135248

show subpopulations

Gnomad AFR exome

AF:

0.0562

Gnomad AMR exome

AF:

0.00234

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000256

Gnomad OTH exome

AF:

0.00230

GnomAD4 exome

AF:

0.00165

AC:

2231

AN:

1351622

Hom.:

Cov.:

AF XY:

0.00146

AC XY:

991

AN XY:

679062

show subpopulations

Gnomad4 AFR exome

AF:

0.0557

Gnomad4 AMR exome

AF:

0.00247

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000226

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000111

Gnomad4 OTH exome

AF:

0.00355

GnomAD4 genome

AF:

0.0152

AC:

2312

AN:

152338

Hom.:

Cov.:

AF XY:

0.0153

AC XY:

1139

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.0529

Gnomad4 AMR

AF:

0.00425

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.00852

Hom.:

Bravo

AF:

0.0174

Asia WGS

AF:

0.00520

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Hermansky-Pudlak syndrome 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

8.4

DANN

Benign

0.88

BranchPoint Hunter

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over