rs225277

Variant names:

• chr17-35646292-G-A
• rs225277
• NM_001030006.2:c.1537-4238G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001030006.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP2B1	NM_001030006.2	MANE Select	c.1537-4238G>A		intron	N/A	NP_001025177.1
	AP2B1	NM_001282.3		c.1537-4238G>A		intron	N/A	NP_001273.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP2B1	ENST00000610402.5	TSL:1 MANE Select	c.1537-4238G>A		intron	N/A	ENSP00000483185.1
	AP2B1	ENST00000618940.4	TSL:1	c.1537-4238G>A		intron	N/A	ENSP00000482835.1
	AP2B1	ENST00000621914.4	TSL:1	c.1537-4238G>A		intron	N/A	ENSP00000482315.1

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

African (AFR) AF: 0.604 AC: 25010 AN: 41404

American (AMR) AF: 0.612 AC: 9340 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1753 AN: 3468

East Asian (EAS) AF: 0.624 AC: 3223 AN: 5162

South Asian (SAS) AF: 0.545 AC: 2631 AN: 4824

European-Finnish (FIN) AF: 0.653 AC: 6885 AN: 10548

Middle Eastern (MID) AF: 0.565 AC: 165 AN: 292

European-Non Finnish (NFE) AF: 0.649 AC: 44121 AN: 67966

Other (OTH) AF: 0.597 AC: 1260 AN: 2112

Alfa AF: 0.632 Hom.: 10821

Bravo AF: 0.617

Asia WGS AF: 0.551 AC: 1915 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.8
DANN	Benign	0.48
PhyloP100		0.51
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: rs225277; hg19: chr17-33973311;