chr5-78128141-A-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_003664.5(AP3B1):c.1857T>G(p.Leu619Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00237 in 1,608,940 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 8 hom. )

Consequence

AP3B1
NM_003664.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 1.83

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 5-78128141-A-C is Benign according to our data. Variant chr5-78128141-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 354235.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-78128141-A-C is described in Lovd as [Benign]. Variant chr5-78128141-A-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=1.83 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00191 (291/152264) while in subpopulation NFE AF= 0.0029 (197/67986). AF 95% confidence interval is 0.00257. There are 1 homozygotes in gnomad4. There are 134 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AP3B1	NM_003664.5 link	c.1857T>G	p.Leu619Leu	synonymous_variant	Exon 17 of 27	ENST00000255194.11	NP_003655.3	O00203-1A0A0S2Z5J4
AP3B1	NM_001271769.2 link	c.1710T>G	p.Leu570Leu	synonymous_variant	Exon 17 of 27		NP_001258698.1	O00203-3A0A0S2Z5J4
AP3B1	NM_001410752.1 link	c.1857T>G	p.Leu619Leu	synonymous_variant	Exon 17 of 23		NP_001397681.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP3B1	ENST00000255194.11 link	c.1857T>G	p.Leu619Leu	synonymous_variant	Exon 17 of 27	1	NM_003664.5	ENSP00000255194.7		O00203-1

Frequencies

GnomAD3 genomes

AF:

0.00191

AC:

291

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.000983

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00584

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00290

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00213

AC:

534

AN:

251126

Hom.:

AF XY:

0.00224

AC XY:

304

AN XY:

135752

show subpopulations

Gnomad AFR exome

AF:

0.000616

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000556

Gnomad FIN exome

AF:

0.00620

Gnomad NFE exome

AF:

0.00314

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.00242

AC:

3529

AN:

1456676

Hom.:

Cov.:

AF XY:

0.00240

AC XY:

1739

AN XY:

724982

show subpopulations

Gnomad4 AFR exome

AF:

0.000330

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000546

Gnomad4 FIN exome

AF:

0.00542

Gnomad4 NFE exome

AF:

0.00277

Gnomad4 OTH exome

AF:

0.00163

GnomAD4 genome

AF:

0.00191

AC:

291

AN:

152264

Hom.:

Cov.:

AF XY:

0.00180

AC XY:

134

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.000981

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00584

Gnomad4 NFE

AF:

0.00290

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00270

Hom.:

Bravo

AF:

0.00148

EpiCase

AF:

0.00234

EpiControl

AF:

0.00219

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

May 09, 2016

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Hermansky-Pudlak syndrome 2

Benign:3

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 20, 2019

Johns Hopkins Genomics, Johns Hopkins University

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Oct 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

AP3B1: BP4, BP7 -

Autoinflammatory syndrome

Benign:1

Jul 01, 2020

Genome Diagnostics Laboratory, The Hospital for Sick Children

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

-0.64

CADD

Benign

5.5

DANN

Benign

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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