chr5-78002795-A-T

Variant names:

• chr5-78002795-A-T
• rs11552314
• NM_003664.5:c.*107T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003664.5(AP3B1):​c.*107T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,242,656 control chromosomes in the GnomAD database, including 41,333 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (7471 hom., cov: 32)
  • Exomes 𝑓: 0.24 (33862 hom.)
• Consequence: AP3B1 NM_003664.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.30
• Publications: 10 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 5-78002795-A-T is Benign according to our data. Variant chr5-78002795-A-T is described in ClinVar as [Benign]. Clinvar id is 354217.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AP3B1	NM_003664.5	c.*107T>A		3_prime_UTR_variant	Exon 27 of 27	ENST00000255194.11	NP_003655.3
AP3B1	NM_001271769.2	c.*107T>A		3_prime_UTR_variant	Exon 27 of 27		NP_001258698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP3B1	ENST00000255194.11	c.*107T>A		3_prime_UTR_variant	Exon 27 of 27	1	NM_003664.5	ENSP00000255194.7

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44715 AN: 152002 Hom.: 7440 Cov.: 32

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.300

GnomAD4 exome AF: 0.238 AC: 259595 AN: 1090536 Hom.: 33862 Cov.: 15 AF XY: 0.233 AC XY: 130487 AN XY: 559592

African (AFR) AF: 0.429 AC: 11235 AN: 26172

American (AMR) AF: 0.457 AC: 20180 AN: 44138

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 4166 AN: 23828

East Asian (EAS) AF: 0.303 AC: 11505 AN: 37966

South Asian (SAS) AF: 0.173 AC: 13595 AN: 78778

European-Finnish (FIN) AF: 0.149 AC: 7863 AN: 52864

Middle Eastern (MID) AF: 0.182 AC: 811 AN: 4452

European-Non Finnish (NFE) AF: 0.231 AC: 178576 AN: 774200

Other (OTH) AF: 0.242 AC: 11664 AN: 48138

GnomAD4 genome AF: 0.294 AC: 44796 AN: 152120 Hom.: 7471 Cov.: 32 AF XY: 0.292 AC XY: 21730 AN XY: 74366

African (AFR) AF: 0.426 AC: 17674 AN: 41470

American (AMR) AF: 0.415 AC: 6343 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 577 AN: 3470

East Asian (EAS) AF: 0.287 AC: 1484 AN: 5178

South Asian (SAS) AF: 0.182 AC: 878 AN: 4830

European-Finnish (FIN) AF: 0.138 AC: 1460 AN: 10594

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15459 AN: 67996

Other (OTH) AF: 0.303 AC: 639 AN: 2106

Alfa AF: 0.253 Hom.: 676

Bravo AF: 0.321

Asia WGS AF: 0.293 AC: 1020 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 25% of patients studied by a panel of primary immunodeficiencies. Number of patients: 24. Only high quality variants are reported. -

Hermansky-Pudlak syndrome Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: 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	-0.53
CADD	Benign	9.1
DANN	Benign	0.85
PhyloP100		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs11552314; hg19: chr5-77298619; COSMIC: COSV54878566; COSMIC: COSV54878566;