rs226088

chr17-35690325-A-Gchr17-35690325-A-T

Variant summary

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

The NM_001030006.2(AP2B1):c.2454+7501A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 152,034 control chromosomes in the GnomAD database, including 9,897 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 0.36 (9897 hom., cov: 32)
• Consequence: AP2B1 NM_001030006.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AP2B1	NM_001030006.2	c.2454+7501A>G		intron_variant		ENST00000610402.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AP2B1	ENST00000610402.5	c.2454+7501A>G		intron_variant		1	NM_001030006.2	P1

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54236 AN: 151916 Hom.: 9876 Cov.: 32

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.357 AC: 54304 AN: 152034 Hom.: 9897 Cov.: 32 AF XY: 0.355 AC XY: 26370 AN XY: 74322

Gnomad4 AFR AF: 0.416

Gnomad4 AMR AF: 0.351

Gnomad4 ASJ AF: 0.391

Gnomad4 EAS AF: 0.447

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.315

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.370

Alfa AF: 0.198 Hom.: 381

Bravo AF: 0.367

Asia WGS AF: 0.376 AC: 1311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.13
Dann	Benign	0.47

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: rs226088; hg19: chr17-34017344;