Variant 15-43475576-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000382044.9(TP53BP1):c.1074C>G(p.Asp358Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 1,613,084 control chromosomes in the GnomAD database, including 107,421 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.46 ( 21371 hom., cov: 32)

Exomes 𝑓: 0.33 ( 86050 hom. )

Consequence

TP53BP1
ENST00000382044.9 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.167

Variant links:

Genes affected

TP53BP1 (HGNC:11999): (tumor protein p53 binding protein 1) This gene encodes a protein that functions in the DNA double-strand break repair pathway choice, promoting non-homologous end joining (NHEJ) pathways, and limiting homologous recombination. This protein plays multiple roles in the DNA damage response, including promoting checkpoint signaling following DNA damage, acting as a scaffold for recruitment of DNA damage response proteins to damaged chromatin, and promoting NHEJ pathways by limiting end resection following a double-strand break. These roles are also important during V(D)J recombination, class switch recombination and at unprotected telomeres. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2017]

TP53BP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.580964E-7).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TP53BP1	NM_001141980.3 linkuse as main transcript	c.1074C>G	p.Asp358Glu	missense_variant	9/28	ENST00000382044.9	NP_001135452.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TP53BP1	ENST00000382044.9 linkuse as main transcript	c.1074C>G	p.Asp358Glu	missense_variant	9/28	1	NM_001141980.3	ENSP00000371475	P4	Q12888-2

Frequencies

GnomAD3 genomes

AF:

0.463

AC:

70394

AN:

152004

Hom.:

21315

Cov.:

show subpopulations

Gnomad AFR

AF:

0.866

Gnomad AMI

AF:

0.224

Gnomad AMR

AF:

0.364

Gnomad ASJ

AF:

0.396

Gnomad EAS

AF:

0.398

Gnomad SAS

AF:

0.424

Gnomad FIN

AF:

0.208

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.295

Gnomad OTH

AF:

0.429

GnomAD3 exomes

AF:

0.362

AC:

90958

AN:

251344

Hom.:

19410

AF XY:

0.357

AC XY:

48530

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.873

Gnomad AMR exome

AF:

0.318

Gnomad ASJ exome

AF:

0.399

Gnomad EAS exome

AF:

0.414

Gnomad SAS exome

AF:

0.435

Gnomad FIN exome

AF:

0.208

Gnomad NFE exome

AF:

0.302

Gnomad OTH exome

AF:

0.333

GnomAD4 exome

AF:

0.327

AC:

477809

AN:

1460960

Hom.:

86050

Cov.:

AF XY:

0.329

AC XY:

239030

AN XY:

726816

show subpopulations

Gnomad4 AFR exome

AF:

0.891

Gnomad4 AMR exome

AF:

0.320

Gnomad4 ASJ exome

AF:

0.400

Gnomad4 EAS exome

AF:

0.409

Gnomad4 SAS exome

AF:

0.435

Gnomad4 FIN exome

AF:

0.210

Gnomad4 NFE exome

AF:

0.301

Gnomad4 OTH exome

AF:

0.359

GnomAD4 genome

AF:

0.463

AC:

70504

AN:

152124

Hom.:

21371

Cov.:

AF XY:

0.456

AC XY:

33915

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.867

Gnomad4 AMR

AF:

0.364

Gnomad4 ASJ

AF:

0.396

Gnomad4 EAS

AF:

0.398

Gnomad4 SAS

AF:

0.424

Gnomad4 FIN

AF:

0.208

Gnomad4 NFE

AF:

0.295

Gnomad4 OTH

AF:

0.430

Alfa

AF:

0.312

Hom.:

5838

Bravo

AF:

0.494

TwinsUK

AF:

0.297

AC:

1101

ALSPAC

AF:

0.305

AC:

1177

ESP6500AA

AF:

0.850

AC:

3740

ESP6500EA

AF:

0.303

AC:

2604

ExAC

AF:

0.374

AC:

45358

Asia WGS

AF:

0.431

AC:

1501

AN:

3478

EpiCase

AF:

0.314

EpiControl

AF:

0.313

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Benign

0.53

DEOGEN2

Benign

0.075

.;T;T;.;T

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.13

T;T;T;T;T

MetaRNN

Benign

5.6e-7

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.4

.;N;.;.;.

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Uncertain

0.57

PROVEAN

Benign

0.94

N;N;N;N;N

REVEL

Benign

0.23

Sift

Benign

1.0

T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;.

Polyphen

0.0

B;B;.;.;.

Vest4

0.018

MutPred

0.13

.;Gain of glycosylation at T357 (P = 0.2197);.;.;.;

MPC

0.063

ClinPred

0.00061

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.021

gMVP

0.054

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over