rs2278355

Positions:

• chr15-82662403-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001278512.2(AP3B2):​c.2834-151G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 685,728 control chromosomes in the GnomAD database, including 113,205 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 0.54 (22932 hom., cov: 32)
  • Exomes 𝑓: 0.58 (90273 hom.)
• Consequence: AP3B2 NM_001278512.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AP3B2	NM_001278512.2	c.2834-151G>A		intron_variant		ENST00000535359.6
CPEB1-AS1	NR_046096.1	n.1328+12257C>T		intron_variant, non_coding_transcript_variant
AP3B2	NM_001278511.2	c.2681-151G>A		intron_variant
AP3B2	NM_004644.5	c.2777-151G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AP3B2	ENST00000535359.6	c.2834-151G>A		intron_variant		1	NM_001278512.2
CPEB1-AS1	ENST00000560650.1	n.1328+12257C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82650 AN: 151828 Hom.: 22908 Cov.: 32

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.556

GnomAD4 exome AF: 0.579 AC: 309021 AN: 533782 Hom.: 90273 Cov.: 6 AF XY: 0.576 AC XY: 160976 AN XY: 279674

Gnomad4 AFR exome AF: 0.424

Gnomad4 AMR exome AF: 0.624

Gnomad4 ASJ exome AF: 0.596

Gnomad4 EAS exome AF: 0.480

Gnomad4 SAS exome AF: 0.505

Gnomad4 FIN exome AF: 0.539

Gnomad4 NFE exome AF: 0.608

Gnomad4 OTH exome AF: 0.566

GnomAD4 genome AF: 0.544 AC: 82714 AN: 151946 Hom.: 22932 Cov.: 32 AF XY: 0.542 AC XY: 40246 AN XY: 74276

Gnomad4 AFR AF: 0.426

Gnomad4 AMR AF: 0.594

Gnomad4 ASJ AF: 0.596

Gnomad4 EAS AF: 0.514

Gnomad4 SAS AF: 0.513

Gnomad4 FIN AF: 0.545

Gnomad4 NFE AF: 0.608

Gnomad4 OTH AF: 0.557

Alfa AF: 0.590 Hom.: 5881

Bravo AF: 0.549

Asia WGS AF: 0.543 AC: 1886 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.4
DANN	Benign	0.59

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

Other links and lift over

dbSNP: rs2278355; hg19: chr15-83331155;