Variant 5-78002861-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The ENST00000255194.11(AP3B1):c.*41A>G variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0115 in 1,613,294 control chromosomes in the GnomAD database, including 142 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0089 ( 14 hom., cov: 32)

Exomes 𝑓: 0.012 ( 128 hom. )

Consequence

AP3B1
ENST00000255194.11 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.85

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 5-78002861-T-C is Benign according to our data. Variant chr5-78002861-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1207984.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00886 (1349/152322) while in subpopulation NFE AF= 0.0126 (855/68038). AF 95% confidence interval is 0.0119. There are 14 homozygotes in gnomad4. There are 621 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AP3B1	NM_003664.5 linkuse as main transcript	c.*41A>G		3_prime_UTR_variant	27/27	ENST00000255194.11	NP_003655.3
AP3B1	NM_001271769.2 linkuse as main transcript	c.*41A>G		3_prime_UTR_variant	27/27		NP_001258698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AP3B1	ENST00000255194.11 linkuse as main transcript	c.*41A>G		3_prime_UTR_variant	27/27	1	NM_003664.5	ENSP00000255194	P2	O00203-1

Frequencies

GnomAD3 genomes

AF:

0.00886

AC:

1349

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00304

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0118

Gnomad ASJ

AF:

0.0259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.00527

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0126

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00905

AC:

2275

AN:

251436

Hom.:

AF XY:

0.00896

AC XY:

1217

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.00215

Gnomad AMR exome

AF:

0.00844

Gnomad ASJ exome

AF:

0.0229

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00444

Gnomad FIN exome

AF:

0.00508

Gnomad NFE exome

AF:

0.0121

Gnomad OTH exome

AF:

0.0152

GnomAD4 exome

AF:

0.0118

AC:

17248

AN:

1460972

Hom.:

128

Cov.:

AF XY:

0.0116

AC XY:

8449

AN XY:

726864

show subpopulations

Gnomad4 AFR exome

AF:

0.00227

Gnomad4 AMR exome

AF:

0.00986

Gnomad4 ASJ exome

AF:

0.0220

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00486

Gnomad4 FIN exome

AF:

0.00586

Gnomad4 NFE exome

AF:

0.0132

Gnomad4 OTH exome

AF:

0.0115

GnomAD4 genome

AF:

0.00886

AC:

1349

AN:

152322

Hom.:

Cov.:

AF XY:

0.00834

AC XY:

621

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00303

Gnomad4 AMR

AF:

0.0118

Gnomad4 ASJ

AF:

0.0259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00394

Gnomad4 FIN

AF:

0.00527

Gnomad4 NFE

AF:

0.0126

Gnomad4 OTH

AF:

0.00993

Alfa

AF:

0.0105

Hom.:

Bravo

AF:

0.00990

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.86

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