rs42360

Positions:

chr5-78116187-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.2016T>C(p.Ala672=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 1,612,438 control chromosomes in the GnomAD database, including 44,621 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4353 hom., cov: 32)

Exomes 𝑓: 0.23 ( 40268 hom. )

Consequence

AP3B1
ENST00000255194.11 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.738

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 5-78116187-A-G is Benign according to our data. Variant chr5-78116187-A-G is described in ClinVar as [Benign]. Clinvar id is 162752.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-78116187-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.738 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.303 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.2016T>C	p.Ala672=	synonymous_variant	18/27	ENST00000255194.11	NP_003655.3
AP3B1	NM_001271769.2 linkuse as main transcript	c.1869T>C	p.Ala623=	synonymous_variant	18/27		NP_001258698.1
AP3B1	NM_001410752.1 linkuse as main transcript	c.2016T>C	p.Ala672=	synonymous_variant	18/23		NP_001397681.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AP3B1	ENST00000255194.11 linkuse as main transcript	c.2016T>C	p.Ala672=	synonymous_variant	18/27	1	NM_003664.5	ENSP00000255194	P2	O00203-1

Frequencies

GnomAD3 genomes

AF:

0.233

AC:

35496

AN:

152032

Hom.:

4349

Cov.:

show subpopulations

Gnomad AFR

AF:

0.256

Gnomad AMI

AF:

0.164

Gnomad AMR

AF:

0.310

Gnomad ASJ

AF:

0.165

Gnomad EAS

AF:

0.0703

Gnomad SAS

AF:

0.131

Gnomad FIN

AF:

0.169

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.238

Gnomad OTH

AF:

0.230

GnomAD3 exomes

AF:

0.213

AC:

53518

AN:

251274

Hom.:

6284

AF XY:

0.205

AC XY:

27822

AN XY:

135822

show subpopulations

Gnomad AFR exome

AF:

0.262

Gnomad AMR exome

AF:

0.315

Gnomad ASJ exome

AF:

0.181

Gnomad EAS exome

AF:

0.0598

Gnomad SAS exome

AF:

0.126

Gnomad FIN exome

AF:

0.176

Gnomad NFE exome

AF:

0.233

Gnomad OTH exome

AF:

0.221

GnomAD4 exome

AF:

0.229

AC:

334316

AN:

1460288

Hom.:

40268

Cov.:

AF XY:

0.225

AC XY:

163524

AN XY:

726512

show subpopulations

Gnomad4 AFR exome

AF:

0.261

Gnomad4 AMR exome

AF:

0.311

Gnomad4 ASJ exome

AF:

0.182

Gnomad4 EAS exome

AF:

0.0758

Gnomad4 SAS exome

AF:

0.128

Gnomad4 FIN exome

AF:

0.179

Gnomad4 NFE exome

AF:

0.243

Gnomad4 OTH exome

AF:

0.216

GnomAD4 genome

AF:

0.234

AC:

35534

AN:

152150

Hom.:

4353

Cov.:

AF XY:

0.229

AC XY:

17064

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.256

Gnomad4 AMR

AF:

0.310

Gnomad4 ASJ

AF:

0.165

Gnomad4 EAS

AF:

0.0697

Gnomad4 SAS

AF:

0.132

Gnomad4 FIN

AF:

0.169

Gnomad4 NFE

AF:

0.238

Gnomad4 OTH

AF:

0.234

Alfa

AF:

0.233

Hom.:

6925

Bravo

AF:

0.244

Asia WGS

AF:

0.145

AC:

506

AN:

3474

EpiCase

AF:

0.232

EpiControl

AF:

0.233

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 46% of patients studied by a panel of primary immunodeficiencies. Number of patients: 44. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	Ala672Ala in exon 18 of AP3B1: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 25.8% (1135/4406) o f African American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs42360). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2Other:1

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 27, 2018	- -
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. -

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

-0.46

CADD

Benign

6.3

DANN

Benign

0.71

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

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