17-35617036-C-G

Variant names:

• chr17-35617036-C-G
• rs16971217
• NM_001030006.2:c.526-7361C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001030006.2(AP2B1):​c.526-7361C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 152,124 control chromosomes in the GnomAD database, including 3,605 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 0.21 (3605 hom., cov: 31)
• Consequence: AP2B1 NM_001030006.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.453
• Publications: 19 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.328 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP2B1	NM_001030006.2	MANE Select	c.526-7361C>G		intron	N/A	NP_001025177.1	A0A140VJE8
	AP2B1	NM_001282.3		c.526-7361C>G		intron	N/A	NP_001273.1	P63010-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP2B1	ENST00000610402.5	TSL:1 MANE Select	c.526-7361C>G		intron	N/A	ENSP00000483185.1	P63010-2
	AP2B1	ENST00000618940.4	TSL:1	c.526-7361C>G		intron	N/A	ENSP00000482835.1	P63010-2
	AP2B1	ENST00000621914.4	TSL:1	c.526-7361C>G		intron	N/A	ENSP00000482315.1	P63010-1

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32388 AN: 152006 Hom.: 3600 Cov.: 31

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.213 AC: 32426 AN: 152124 Hom.: 3605 Cov.: 31 AF XY: 0.214 AC XY: 15947 AN XY: 74382

African (AFR) AF: 0.266 AC: 11050 AN: 41488

American (AMR) AF: 0.228 AC: 3480 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 861 AN: 3468

East Asian (EAS) AF: 0.341 AC: 1765 AN: 5172

South Asian (SAS) AF: 0.204 AC: 985 AN: 4824

European-Finnish (FIN) AF: 0.177 AC: 1871 AN: 10580

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.173 AC: 11784 AN: 68004

Other (OTH) AF: 0.223 AC: 470 AN: 2110

Alfa AF: 0.191 Hom.: 1642

Bravo AF: 0.223

Asia WGS AF: 0.279 AC: 974 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.6
DANN	Benign	0.64
PhyloP100		-0.45
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: rs16971217; hg19: chr17-33944055;