rs12655917

Variant names:

• chr5-77996116-G-A
• rs12655917
• ENST00000519295.7:c.*6786C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000519295.7(AP3B1):​c.*6786C>T variant causes a 3 prime UTR change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0449 in 152,246 control chromosomes in the GnomAD database, including 289 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.045 (289 hom., cov: 33)
• Consequence: AP3B1 ENST00000519295.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.27
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• Hermansky-Pudlak syndrome 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, G2P

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP3B1	ENST00000519295.7	c.*6786C>T		3_prime_UTR_variant	Exon 27 of 27	1		ENSP00000430597.1

Frequencies

GnomAD3 genomes AF: 0.0449 AC: 6836 AN: 152128 Hom.: 289 Cov.: 33

Gnomad AFR AF: 0.0112

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0963

Gnomad ASJ AF: 0.0701

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.0665

Gnomad FIN AF: 0.0289

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0414

Gnomad OTH AF: 0.0522

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0449 AC: 6839 AN: 152246 Hom.: 289 Cov.: 33 AF XY: 0.0463 AC XY: 3447 AN XY: 74444

African (AFR) AF: 0.0112 AC: 465 AN: 41540

American (AMR) AF: 0.0963 AC: 1473 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0701 AC: 243 AN: 3468

East Asian (EAS) AF: 0.205 AC: 1065 AN: 5186

South Asian (SAS) AF: 0.0662 AC: 319 AN: 4822

European-Finnish (FIN) AF: 0.0289 AC: 306 AN: 10604

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0414 AC: 2817 AN: 68006

Other (OTH) AF: 0.0530 AC: 112 AN: 2112

Alfa AF: 0.0489 Hom.: 883

Bravo AF: 0.0510

Asia WGS AF: 0.147 AC: 511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	20
DANN	Benign	0.92
PhyloP100		7.3

Splicing

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

Other links and lift over

dbSNP: rs12655917; hg19: chr5-77291940;