chr1-223804257-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 11/19 in silico tools predict 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

Publications

16 publications found

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 Gene-Disease associations (from GenCC):

Tourette syndrome
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

TP53BP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 788949.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 6 Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031685.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TP53BP2	NM_001031685.3	MANE Select	c.566C>T	p.Ala189Val	missense	Exon 6 of 18	NP_001026855.2
	TP53BP2	NM_005426.3		c.179C>T	p.Ala60Val	missense	Exon 7 of 19	NP_005417.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TP53BP2	ENST00000343537.12	TSL:1 MANE Select	c.566C>T	p.Ala189Val	missense	Exon 6 of 18	ENSP00000341957.7
TP53BP2	ENST00000391878.6	TSL:1	c.179C>T	p.Ala60Val	missense	Exon 7 of 19	ENSP00000375750.2
TP53BP2	ENST00000494100.1	TSL:3	c.365C>T	p.Ala122Val	missense	Exon 4 of 5	ENSP00000420225.1

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

GnomAD2 exomes

AF:

0.00890

AC:

2237

AN:

251302

AF XY:

0.00885

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 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

African (AFR)

AF:

0.00191

AC:

AN:

33470

American (AMR)

AF:

0.00756

AC:

338

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.0131

AC:

343

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39676

South Asian (SAS)

AF:

0.000962

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.00944

AC:

504

AN:

53416

Middle Eastern (MID)

AF:

0.00537

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0141

AC:

15657

AN:

1111952

Other (OTH)

AF:

0.0110

AC:

666

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

980

1960

2940

3920

4900

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

600

1200

1800

2400

3000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00875

AC:

1332

AN:

152292

Hom.:

Cov.:

AF XY:

0.00782

AC XY:

582

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.00265

AC:

110

AN:

41544

American (AMR)

AF:

0.00804

AC:

123

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0153

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0102

AC:

108

AN:

10612

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0133

AC:

903

AN:

68032

Other (OTH)

AF:

0.0128

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

144

215

287

359

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0117

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

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

TP53BP2-related disorder

Benign:1

Feb 20, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.51

CADD

Uncertain

(source)

DANN

Uncertain

0.99

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.95

MetaRNN

Benign

0.0067

MetaSVM

Benign

-1.1

PhyloP100

6.6

PrimateAI

Benign

0.48

PROVEAN

Benign

1.1

REVEL

Benign

0.17

Sift

Benign

1.0

Sift4G

Benign

1.0

Vest4

0.41

MVP

0.69

MPC

0.70

ClinPred

0.038

GERP RS

5.3

gMVP

0.19

Mutation Taster

=93/7

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over