15-82687507-A-G

Variant names:

• chr15-82687507-A-G
• rs8043401
• NM_001278512.2:c.360+1229T>C

Variant summary

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

The NM_001278512.2(AP3B2):​c.360+1229T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 152,130 control chromosomes in the GnomAD database, including 26,103 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 0.58 (26103 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: AP3B2 NM_001278512.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.141
• Publications: 8 publications found

Genes affected

AP3B2 (HGNC:567): (adaptor related protein complex 3 subunit beta 2) Adaptor protein complex 3 (AP-3 complex) is a heterotrimeric protein complex involved in the formation of clathrin-coated synaptic vesicles. The protein encoded by this gene represents the beta subunit of the neuron-specific AP-3 complex and was first identified as the target antigen in human paraneoplastic neurologic disorders. The encoded subunit binds clathrin and is phosphorylated by a casein kinase-like protein, which mediates synaptic vesicle coat assembly. Defects in this gene are a cause of early-onset epileptic encephalopathy. [provided by RefSeq, Feb 2017]

CPEB1-AS1 (HGNC:27523): (CPEB1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AP3B2	NM_001278512.2	c.360+1229T>C		intron_variant	Intron 4 of 26	ENST00000535359.6	NP_001265441.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP3B2	ENST00000535359.6	c.360+1229T>C		intron_variant	Intron 4 of 26	1	NM_001278512.2	ENSP00000440984.1

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88814 AN: 152012 Hom.: 26063 Cov.: 33

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.627

Gnomad OTH AF: 0.579

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.584 AC: 88905 AN: 152130 Hom.: 26103 Cov.: 33 AF XY: 0.583 AC XY: 43329 AN XY: 74368

African (AFR) AF: 0.514 AC: 21333 AN: 41486

American (AMR) AF: 0.614 AC: 9388 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 2150 AN: 3470

East Asian (EAS) AF: 0.537 AC: 2777 AN: 5170

South Asian (SAS) AF: 0.518 AC: 2500 AN: 4822

European-Finnish (FIN) AF: 0.594 AC: 6285 AN: 10582

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.627 AC: 42645 AN: 68002

Other (OTH) AF: 0.581 AC: 1227 AN: 2112

Alfa AF: 0.617 Hom.: 5492

Bravo AF: 0.589

Asia WGS AF: 0.564 AC: 1958 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.0
DANN	Benign	0.60
PhyloP100		0.14
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: rs8043401; hg19: chr15-83356259;