5-78036446-A-G

Variant names:

• chr5-78036446-A-G
• rs3822646
• NM_003664.5:c.2810-2001T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003664.5(AP3B1):​c.2810-2001T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0295 in 152,224 control chromosomes in the GnomAD database, including 163 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 0.030 (163 hom., cov: 32)
• Consequence: AP3B1 NM_003664.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.180
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AP3B1	NM_003664.5	c.2810-2001T>C		intron_variant	Intron 23 of 26	ENST00000255194.11	NP_003655.3
AP3B1	NM_001271769.2	c.2663-2001T>C		intron_variant	Intron 23 of 26		NP_001258698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP3B1	ENST00000255194.11	c.2810-2001T>C		intron_variant	Intron 23 of 26	1	NM_003664.5	ENSP00000255194.7

Frequencies

GnomAD3 genomes AF: 0.0295 AC: 4492 AN: 152106 Hom.: 163 Cov.: 32

Gnomad AFR AF: 0.0174

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0892

Gnomad ASJ AF: 0.0271

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.0482

Gnomad FIN AF: 0.0187

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0162

Gnomad OTH AF: 0.0330

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

GnomAD4 genome AF: 0.0295 AC: 4494 AN: 152224 Hom.: 163 Cov.: 32 AF XY: 0.0316 AC XY: 2350 AN XY: 74422

African (AFR) AF: 0.0174 AC: 723 AN: 41550

American (AMR) AF: 0.0891 AC: 1362 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0271 AC: 94 AN: 3470

East Asian (EAS) AF: 0.137 AC: 712 AN: 5180

South Asian (SAS) AF: 0.0479 AC: 231 AN: 4826

European-Finnish (FIN) AF: 0.0187 AC: 198 AN: 10606

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0162 AC: 1101 AN: 67988

Other (OTH) AF: 0.0327 AC: 69 AN: 2112

Alfa AF: 0.0328 Hom.: 87

Bravo AF: 0.0358

Asia WGS AF: 0.105 AC: 365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.66
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3822646; hg19: chr5-77332270;