Variant rs61749337 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001031685.3(TP53BP2):c.566C>T(p.Ala189Val) variant causes a missense change. The variant allele was found at a frequency of 0.0118 in 1,614,044 control chromosomes in the GnomAD database, including 156 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0087 ( 6 hom., cov: 32)

Exomes 𝑓: 0.012 ( 150 hom. )

Consequence

TP53BP2
NM_001031685.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 6.60

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0067211688).

BP6

Variant 1-223804257-G-A is Benign according to our data. Variant chr1-223804257-G-A is described in ClinVar as [Benign]. Clinvar id is 788949.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TP53BP2	NM_001031685.3 link	c.566C>T	p.Ala189Val	missense_variant	6/18	ENST00000343537.12	NP_001026855.2	Q13625-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TP53BP2	ENST00000343537.12 link	c.566C>T	p.Ala189Val	missense_variant	6/18	1	NM_001031685.3	ENSP00000341957.7	Q13625-3
TP53BP2	ENST00000391878.6 link	c.179C>T	p.Ala60Val	missense_variant	7/19	1		ENSP00000375750.2	Q13625-2
TP53BP2	ENST00000494100.1 link	c.365C>T	p.Ala122Val	missense_variant	4/5	3		ENSP00000420225.1	H7C5L8
TP53BP2	ENST00000496282.5 link	n.459C>T		non_coding_transcript_exon_variant	5/5	3

Frequencies

GnomAD3 genomes

AF:

0.00876

AC:

1333

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00266

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00805

Gnomad ASJ

AF:

0.0153

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0102

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0133

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.00890

AC:

2237

AN:

251302

Hom.:

AF XY:

0.00885

AC XY:

1202

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.00283

Gnomad AMR exome

AF:

0.00739

Gnomad ASJ exome

AF:

0.0122

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000850

Gnomad FIN exome

AF:

0.0102

Gnomad NFE exome

AF:

0.0131

Gnomad OTH exome

AF:

0.0122

GnomAD4 exome

AF:

0.0121

AC:

17686

AN:

1461752

Hom.:

150

Cov.:

AF XY:

0.0117

AC XY:

8483

AN XY:

727162

show subpopulations

Gnomad4 AFR exome

AF:

0.00191

Gnomad4 AMR exome

AF:

0.00756

Gnomad4 ASJ exome

AF:

0.0131

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000962

Gnomad4 FIN exome

AF:

0.00944

Gnomad4 NFE exome

AF:

0.0141

Gnomad4 OTH exome

AF:

0.0110

GnomAD4 genome

AF:

0.00875

AC:

1332

AN:

152292

Hom.:

Cov.:

AF XY:

0.00782

AC XY:

582

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00265

Gnomad4 AMR

AF:

0.00804

Gnomad4 ASJ

AF:

0.0153

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0102

Gnomad4 NFE

AF:

0.0133

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.0119

Hom.:

Bravo

AF:

0.00858

TwinsUK

AF:

0.0146

AC:

ALSPAC

AF:

0.0184

AC:

ESP6500AA

AF:

0.00295

AC:

ESP6500EA

AF:

0.0136

AC:

117

ExAC

AF:

0.00825

AC:

1001

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

TP53BP2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 20, 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

-0.52

BayesDel_noAF

Benign

-0.51

CADD

Uncertain

DANN

Uncertain

0.99

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.95

D;D

MetaRNN

Benign

0.0067

T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.48

PROVEAN

Benign

1.1

N;N

REVEL

Benign

0.17

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Vest4

0.41

MVP

0.69

MPC

0.70

ClinPred

0.038

GERP RS

5.3

gMVP

0.19

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

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