rs2278355

Variant names:

• chr15-82662403-C-T
• rs2278355
• NM_001278512.2:c.2834-151G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278512.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP3B2	NM_001278512.2	MANE Select	c.2834-151G>A		intron	N/A	NP_001265441.1	Q13367-4
	AP3B2	NM_004644.5		c.2777-151G>A		intron	N/A	NP_004635.2
	AP3B2	NM_001278511.2		c.2681-151G>A		intron	N/A	NP_001265440.1	Q13367-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP3B2	ENST00000535359.6	TSL:1 MANE Select	c.2834-151G>A		intron	N/A	ENSP00000440984.1	Q13367-4
	AP3B2	ENST00000261722.8	TSL:1	c.2795-151G>A		intron	N/A	ENSP00000261722.4	A0A5F9UJV3
	AP3B2	ENST00000535348.5	TSL:1	c.2681-151G>A		intron	N/A	ENSP00000438721.1	Q13367-3

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

African (AFR) AF: 0.424 AC: 6058 AN: 14286

American (AMR) AF: 0.624 AC: 14336 AN: 22964

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 8916 AN: 14968

East Asian (EAS) AF: 0.480 AC: 15163 AN: 31600

South Asian (SAS) AF: 0.505 AC: 24672 AN: 48870

European-Finnish (FIN) AF: 0.539 AC: 20343 AN: 37754

Middle Eastern (MID) AF: 0.541 AC: 1209 AN: 2234

European-Non Finnish (NFE) AF: 0.608 AC: 202000 AN: 332250

Other (OTH) AF: 0.566 AC: 16324 AN: 28856

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

African (AFR) AF: 0.426 AC: 17629 AN: 41426

American (AMR) AF: 0.594 AC: 9071 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 2069 AN: 3472

East Asian (EAS) AF: 0.514 AC: 2642 AN: 5140

South Asian (SAS) AF: 0.513 AC: 2475 AN: 4820

European-Finnish (FIN) AF: 0.545 AC: 5753 AN: 10548

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.608 AC: 41310 AN: 67950

Other (OTH) AF: 0.557 AC: 1177 AN: 2112

Alfa AF: 0.587 Hom.: 5965

Bravo AF: 0.549

Asia WGS AF: 0.543 AC: 1886 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.4
DANN	Benign	0.59
PhyloP100		0.089
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: rs2278355; hg19: chr15-83331155; COSMIC: COSV107234994; COSMIC: COSV107234994;