rs11638815

chr15-82683530-A-Cchr15-82683530-A-T

Variant summary

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

The NM_001278512.2(AP3B2):c.361-1950T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,136 control chromosomes in the GnomAD database, including 3,691 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 0.20 (3691 hom., cov: 32)
• Consequence: AP3B2 NM_001278512.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.429

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AP3B2	NM_001278512.2	c.361-1950T>G		intron_variant		ENST00000535359.6
CPEB1-AS1	NR_046096.1	n.1329-8481A>C		intron_variant, non_coding_transcript_variant
AP3B2	NM_001278511.2	c.265-1950T>G		intron_variant
AP3B2	NM_004644.5	c.361-1950T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AP3B2	ENST00000535359.6	c.361-1950T>G		intron_variant		1	NM_001278512.2
CPEB1-AS1	ENST00000560650.1	n.1329-8481A>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30131 AN: 152018 Hom.: 3679 Cov.: 32

Gnomad AFR AF: 0.0504

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.198 AC: 30163 AN: 152136 Hom.: 3691 Cov.: 32 AF XY: 0.202 AC XY: 15029 AN XY: 74360

Gnomad4 AFR AF: 0.0502

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.203

Gnomad4 SAS AF: 0.343

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.249

Gnomad4 OTH AF: 0.208

Alfa AF: 0.159 Hom.: 484

Bravo AF: 0.196

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	4.1
Dann	Benign	0.71

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: rs11638815; hg19: chr15-83352282;