rs4532349

Positions:

chr5-78177341-A-G

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The ENST00000255194.11(AP3B1):c.1038T>C(p.Asn346=) 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
ENST00000255194.11 splice_region, synonymous

Scores

Splicing: ADA: 0.001395

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7O:1

Conservation

PhyloP100: 3.11

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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. Variant chr5-78177341-A-G is described in Lovd as [Benign].

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/exons	MANE	Protein
AP3B1	NM_003664.5 linkuse as main transcript	c.1038T>C	p.Asn346=	splice_region_variant, synonymous_variant	9/27	ENST00000255194.11	NP_003655.3
AP3B1	NM_001271769.2 linkuse as main transcript	c.891T>C	p.Asn297=	splice_region_variant, synonymous_variant	9/27		NP_001258698.1
AP3B1	NM_001410752.1 linkuse as main transcript	c.1038T>C	p.Asn346=	splice_region_variant, synonymous_variant	9/23		NP_001397681.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AP3B1	ENST00000255194.11 linkuse as main transcript	c.1038T>C	p.Asn346=	splice_region_variant, synonymous_variant	9/27	1	NM_003664.5	ENSP00000255194	P2	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

GnomAD3 exomes

AF:

0.194

AC:

48604

AN:

251172

Hom.:

5258

AF XY:

0.188

AC XY:

25543

AN XY:

135744

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 SAS exome

AF:

0.118

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

Gnomad4 AFR exome

AF:

0.103

Gnomad4 AMR exome

AF:

0.293

Gnomad4 ASJ exome

AF:

0.173

Gnomad4 EAS exome

AF:

0.0748

Gnomad4 SAS exome

AF:

0.120

Gnomad4 FIN exome

AF:

0.175

Gnomad4 NFE exome

AF:

0.230

Gnomad4 OTH exome

AF:

0.196

GnomAD4 genome

AF:

0.184

AC:

27972

AN:

152138

Hom.:

2847

Cov.:

AF XY:

0.182

AC XY:

13499

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.115

Gnomad4 AMR

AF:

0.271

Gnomad4 ASJ

AF:

0.156

Gnomad4 EAS

AF:

0.0688

Gnomad4 SAS

AF:

0.125

Gnomad4 FIN

AF:

0.165

Gnomad4 NFE

AF:

0.224

Gnomad4 OTH

AF:

0.187

Alfa

AF:

0.212

Hom.:

4525

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:7Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Nov 12, 2023	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jun 13, 2013	Benign based on MAF (12-22% in ESP populations) -

not provided

Benign:2Other:1

not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	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. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 27, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Hermansky-Pudlak syndrome 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Hermansky-Pudlak syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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