rs367638774

Variant names:

• chr15-82659602-G-A
• rs367638774
• NM_001278512.2:c.3264C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-82659602-G-A
• chr15-82659602-G-C

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS1

The NM_001278512.2(AP3B2):​c.3264C>T​(p.Gly1088Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,613,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: AP3B2 NM_001278512.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.605
• Publications: 1 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 15-82659602-G-A is Benign according to our data. Variant chr15-82659602-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1675019.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.605 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000151 (23/152148) while in subpopulation AFR AF = 0.000531 (22/41426). AF 95% confidence interval is 0.000359. There are 0 homozygotes in GnomAd4. There are 13 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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.3264C>T	p.Gly1088Gly	synonymous	Exon 27 of 27	NP_001265441.1	Q13367-4
	AP3B2	NM_004644.5		c.3207C>T	p.Gly1069Gly	synonymous	Exon 26 of 26	NP_004635.2
	AP3B2	NM_001278511.2		c.3111C>T	p.Gly1037Gly	synonymous	Exon 25 of 25	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.3264C>T	p.Gly1088Gly	synonymous	Exon 27 of 27	ENSP00000440984.1	Q13367-4
	AP3B2	ENST00000261722.8	TSL:1	c.3225C>T	p.Gly1075Gly	synonymous	Exon 26 of 26	ENSP00000261722.4	A0A5F9UJV3
	AP3B2	ENST00000535348.5	TSL:1	c.3111C>T	p.Gly1037Gly	synonymous	Exon 25 of 25	ENSP00000438721.1	Q13367-3

Frequencies

GnomAD3 genomes AF: 0.000151 AC: 23 AN: 152148 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000401 AC: 10 AN: 249222 AF XY: 0.0000222

Gnomad AFR exome AF: 0.000581

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000253 AC: 37 AN: 1461666 Hom.: 0 Cov.: 31 AF XY: 0.0000179 AC XY: 13 AN XY: 727132

African (AFR) AF: 0.000926 AC: 31 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111864

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome AF: 0.000151 AC: 23 AN: 152148 Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13 AN XY: 74328

African (AFR) AF: 0.000531 AC: 22 AN: 41426

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.000253

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_noAF	Benign	-0.42
CADD	Benign	4.5
DANN	Benign	0.83
PhyloP100		0.60

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: rs367638774; hg19: chr15-83328354; COSMIC: COSV55607664; COSMIC: COSV55607664;