Variant rs34683843 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001031685.3(TP53BP2):c.685C>A(p.Gln229Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0814 in 1,613,248 control chromosomes in the GnomAD database, including 5,962 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.061 ( 378 hom., cov: 32)

Exomes 𝑓: 0.084 ( 5584 hom. )

Consequence

TP53BP2
NM_001031685.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 9.57

Variant links:

Genes affected

TP53BP2 (HGNC:12000): (tumor protein p53 binding protein 2) This gene encodes a member of the ASPP (apoptosis-stimulating protein of p53) family of p53 interacting proteins. The protein contains four ankyrin repeats and an SH3 domain involved in protein-protein interactions. It is localized to the perinuclear region of the cytoplasm, and regulates apoptosis and cell growth through interactions with other regulatory molecules including members of the p53 family. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

TP53BP2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0053198636).

BP6

Variant 1-223803417-G-T is Benign according to our data. Variant chr1-223803417-G-T is described in ClinVar as [Benign]. Clinvar id is 3057025.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TP53BP2	NM_001031685.3 linkuse as main transcript	c.685C>A	p.Gln229Lys	missense_variant	7/18	ENST00000343537.12	NP_001026855.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TP53BP2	ENST00000343537.12 linkuse as main transcript	c.685C>A	p.Gln229Lys	missense_variant	7/18	1	NM_001031685.3	ENSP00000341957	P1	Q13625-3
TP53BP2	ENST00000391878.6 linkuse as main transcript	c.298C>A	p.Gln100Lys	missense_variant	8/19	1		ENSP00000375750		Q13625-2
TP53BP2	ENST00000494100.1 linkuse as main transcript	c.415+791C>A		intron_variant		3		ENSP00000420225

Frequencies

GnomAD3 genomes

AF:

0.0610

AC:

9276

AN:

152048

Hom.:

378

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0171

Gnomad AMI

AF:

0.0877

Gnomad AMR

AF:

0.0456

Gnomad ASJ

AF:

0.0740

Gnomad EAS

AF:

0.0191

Gnomad SAS

AF:

0.0521

Gnomad FIN

AF:

0.0924

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0891

Gnomad OTH

AF:

0.0575

GnomAD3 exomes

AF:

0.0659

AC:

16509

AN:

250604

Hom.:

694

AF XY:

0.0677

AC XY:

9175

AN XY:

135482

show subpopulations

Gnomad AFR exome

AF:

0.0127

Gnomad AMR exome

AF:

0.0359

Gnomad ASJ exome

AF:

0.0754

Gnomad EAS exome

AF:

0.0161

Gnomad SAS exome

AF:

0.0526

Gnomad FIN exome

AF:

0.0852

Gnomad NFE exome

AF:

0.0894

Gnomad OTH exome

AF:

0.0715

GnomAD4 exome

AF:

0.0835

AC:

122018

AN:

1461082

Hom.:

5584

Cov.:

AF XY:

0.0829

AC XY:

60247

AN XY:

726862

show subpopulations

Gnomad4 AFR exome

AF:

0.0145

Gnomad4 AMR exome

AF:

0.0381

Gnomad4 ASJ exome

AF:

0.0770

Gnomad4 EAS exome

AF:

0.0139

Gnomad4 SAS exome

AF:

0.0546

Gnomad4 FIN exome

AF:

0.0871

Gnomad4 NFE exome

AF:

0.0926

Gnomad4 OTH exome

AF:

0.0755

GnomAD4 genome

AF:

0.0609

AC:

9271

AN:

152166

Hom.:

378

Cov.:

AF XY:

0.0603

AC XY:

4484

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0171

Gnomad4 AMR

AF:

0.0456

Gnomad4 ASJ

AF:

0.0740

Gnomad4 EAS

AF:

0.0191

Gnomad4 SAS

AF:

0.0522

Gnomad4 FIN

AF:

0.0924

Gnomad4 NFE

AF:

0.0891

Gnomad4 OTH

AF:

0.0569

Alfa

AF:

0.0797

Hom.:

486

Bravo

AF:

0.0556

TwinsUK

AF:

0.0793

AC:

294

ALSPAC

AF:

0.104

AC:

401

ESP6500AA

AF:

0.0148

AC:

ESP6500EA

AF:

0.0885

AC:

761

ExAC

AF:

0.0659

AC:

8000

Asia WGS

AF:

0.0280

AC:

AN:

3478

EpiCase

AF:

0.0938

EpiControl

AF:

0.0912

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TP53BP2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 30, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.33

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Pathogenic

0.92

Eigen_PC

Pathogenic

0.94

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.97

D;D

MetaRNN

Benign

0.0053

T;T

MetaSVM

Benign

-1.2

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.24

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0080

D;D

Vest4

0.45

MPC

0.78

ClinPred

0.022

GERP RS

6.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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