rs225277

Positions:

• chr17-35646292-G-A

Variant summary

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

The NM_001030006.2(AP2B1):​c.1537-4238G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 151,956 control chromosomes in the GnomAD database, including 29,704 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 0.62 (29704 hom., cov: 31)
• Consequence: AP2B1 NM_001030006.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.505

Genes affected

AP2B1 (HGNC:563): (adaptor related protein complex 2 subunit beta 1) The protein encoded by this gene is one of two large chain components of the assembly protein complex 2, which serves to link clathrin to receptors in coated vesicles. The encoded protein is found on the cytoplasmic face of coated vesicles in the plasma membrane. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AP2B1	NM_001030006.2	c.1537-4238G>A		intron_variant		ENST00000610402.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AP2B1	ENST00000610402.5	c.1537-4238G>A		intron_variant		1	NM_001030006.2	P1

Frequencies

GnomAD3 genomes AF: 0.625 AC: 94917 AN: 151838 Hom.: 29708 Cov.: 31

Gnomad AFR AF: 0.605

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.626

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.601

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

GnomAD4 genome AF: 0.625 AC: 94949 AN: 151956 Hom.: 29704 Cov.: 31 AF XY: 0.624 AC XY: 46335 AN XY: 74256

Gnomad4 AFR AF: 0.604

Gnomad4 AMR AF: 0.612

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.624

Gnomad4 SAS AF: 0.545

Gnomad4 FIN AF: 0.653

Gnomad4 NFE AF: 0.649

Gnomad4 OTH AF: 0.597

Alfa AF: 0.634 Hom.: 5661

Bravo AF: 0.617

Asia WGS AF: 0.551 AC: 1915 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.8
DANN	Benign	0.48

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: rs225277; hg19: chr17-33973311;