Genetic Variant NM_001031685.3:c.*602G>A (chr1-223780251-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001031685.3(TP53BP2):c.*602G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 152,110 control chromosomes in the GnomAD database, including 10,500 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 0.31 ( 10500 hom., cov: 33)

Exomes 𝑓: 0.25 ( 0 hom. )

Consequence

TP53BP2
NM_001031685.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.14

Publications

20 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TP53BP2	NM_001031685.3 link	c.*602G>A		3_prime_UTR_variant	Exon 18 of 18	ENST00000343537.12	NP_001026855.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TP53BP2	ENST00000343537.12 link	c.*602G>A		3_prime_UTR_variant	Exon 18 of 18	1	NM_001031685.3	ENSP00000341957.7
TP53BP2	ENST00000391878.6 link	c.*602G>A		3_prime_UTR_variant	Exon 19 of 19	1		ENSP00000375750.2

Frequencies

GnomAD3 genomes

AF:

0.307

AC:

46645

AN:

151984

Hom.:

10473

Cov.:

show subpopulations

Gnomad AFR

AF:

0.637

Gnomad AMI

AF:

0.109

Gnomad AMR

AF:

0.273

Gnomad ASJ

AF:

0.186

Gnomad EAS

AF:

0.333

Gnomad SAS

AF:

0.151

Gnomad FIN

AF:

0.131

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.160

Gnomad OTH

AF:

0.290

GnomAD4 exome

AF:

0.250

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.307

AC:

46732

AN:

152102

Hom.:

10500

Cov.:

AF XY:

0.303

AC XY:

22497

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.637

AC:

26442

AN:

41494

American (AMR)

AF:

0.273

AC:

4175

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.186

AC:

645

AN:

3468

East Asian (EAS)

AF:

0.332

AC:

1717

AN:

5172

South Asian (SAS)

AF:

0.150

AC:

725

AN:

4822

European-Finnish (FIN)

AF:

0.131

AC:

1379

AN:

10562

Middle Eastern (MID)

AF:

0.221

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.160

AC:

10868

AN:

67984

Other (OTH)

AF:

0.292

AC:

617

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1345

2689

4034

5378

6723

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

422

844

1266

1688

2110

<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:

0.208

Hom.:

5572

Bravo

AF:

0.336

Asia WGS

AF:

0.268

AC:

932

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

5.0

(source)

DANN

Benign

0.47

PhyloP100

1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over