Variant 1-223784160-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_001031685.3(TP53BP2):c.3318G>A(p.Ala1106Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0195 in 1,614,086 control chromosomes in the GnomAD database, including 428 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.017 ( 37 hom., cov: 32)

Exomes 𝑓: 0.020 ( 391 hom. )

Consequence

TP53BP2
NM_001031685.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.29

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 1-223784160-C-T is Benign according to our data. Variant chr1-223784160-C-T is described in ClinVar as [Benign]. Clinvar id is 3041533.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-2.29 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0168 (2551/152266) while in subpopulation NFE AF= 0.0228 (1548/68020). AF 95% confidence interval is 0.0218. There are 37 homozygotes in gnomad4. There are 1316 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 37 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TP53BP2	NM_001031685.3 link	c.3318G>A	p.Ala1106Ala	synonymous_variant	17/18	ENST00000343537.12	NP_001026855.2	Q13625-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TP53BP2	ENST00000343537.12 link	c.3318G>A	p.Ala1106Ala	synonymous_variant	17/18	1	NM_001031685.3	ENSP00000341957.7		Q13625-3

Frequencies

GnomAD3 genomes

AF:

0.0168

AC:

2554

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00299

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.0122

Gnomad ASJ

AF:

0.0231

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.0509

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0228

Gnomad OTH

AF:

0.0187

GnomAD3 exomes

AF:

0.0190

AC:

4782

AN:

251424

Hom.:

AF XY:

0.0187

AC XY:

2544

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.00332

Gnomad AMR exome

AF:

0.00824

Gnomad ASJ exome

AF:

0.0200

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00444

Gnomad FIN exome

AF:

0.0475

Gnomad NFE exome

AF:

0.0260

Gnomad OTH exome

AF:

0.0201

GnomAD4 exome

AF:

0.0198

AC:

28971

AN:

1461820

Hom.:

391

Cov.:

AF XY:

0.0193

AC XY:

14058

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.00266

Gnomad4 AMR exome

AF:

0.00863

Gnomad4 ASJ exome

AF:

0.0226

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00466

Gnomad4 FIN exome

AF:

0.0488

Gnomad4 NFE exome

AF:

0.0214

Gnomad4 OTH exome

AF:

0.0180

GnomAD4 genome

AF:

0.0168

AC:

2551

AN:

152266

Hom.:

Cov.:

AF XY:

0.0177

AC XY:

1316

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00298

Gnomad4 AMR

AF:

0.0122

Gnomad4 ASJ

AF:

0.0231

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.0509

Gnomad4 NFE

AF:

0.0228

Gnomad4 OTH

AF:

0.0185

Alfa

AF:

0.0211

Hom.:

Bravo

AF:

0.0133

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0198

EpiControl

AF:

0.0220

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

Mar 22, 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_noAF

Benign

-0.62

CADD

Benign

3.9

DANN

Benign

0.57

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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