Variant 17-35624468-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The ENST00000610402.5(AP2B1):c.597G>A(p.Leu199=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00901 in 1,614,120 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0069 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0092 ( 75 hom. )

Consequence

AP2B1
ENST00000610402.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.61

Variant links:

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]

AP2B1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 17-35624468-G-A is Benign according to our data. Variant chr17-35624468-G-A is described in ClinVar as [Benign]. Clinvar id is 773590.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.61 with no splicing effect.

BS2

High AC in GnomAd4 at 1045 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AP2B1	NM_001030006.2 linkuse as main transcript	c.597G>A	p.Leu199=	synonymous_variant	6/22	ENST00000610402.5	NP_001025177.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AP2B1	ENST00000610402.5 linkuse as main transcript	c.597G>A	p.Leu199=	synonymous_variant	6/22	1	NM_001030006.2	ENSP00000483185	P1	P63010-2

Frequencies

GnomAD3 genomes

AF:

0.00686

AC:

1044

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00224

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00844

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00480

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0110

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00590

AC:

1483

AN:

251404

Hom.:

AF XY:

0.00569

AC XY:

773

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.00221

Gnomad AMR exome

AF:

0.00338

Gnomad ASJ exome

AF:

0.00109

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00739

Gnomad NFE exome

AF:

0.00981

Gnomad OTH exome

AF:

0.00684

GnomAD4 exome

AF:

0.00924

AC:

13502

AN:

1461848

Hom.:

Cov.:

AF XY:

0.00888

AC XY:

6459

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00158

Gnomad4 AMR exome

AF:

0.00407

Gnomad4 ASJ exome

AF:

0.00130

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00790

Gnomad4 NFE exome

AF:

0.0111

Gnomad4 OTH exome

AF:

0.00666

GnomAD4 genome

AF:

0.00686

AC:

1045

AN:

152272

Hom.:

Cov.:

AF XY:

0.00628

AC XY:

468

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00224

Gnomad4 AMR

AF:

0.00850

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00480

Gnomad4 NFE

AF:

0.0110

Gnomad4 OTH

AF:

0.00663

Alfa

AF:

0.00853

Hom.:

Bravo

AF:

0.00716

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0109

EpiControl

AF:

0.00978

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over