Variant 15-43469998-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001141980.3(TP53BP1):c.1249G>A(p.Gly417Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 1,613,390 control chromosomes in the GnomAD database, including 33,013 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 0.28 ( 10247 hom., cov: 32)

Exomes 𝑓: 0.14 ( 22766 hom. )

Consequence

TP53BP1
NM_001141980.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.39

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=7.288852E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.644 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.1249G>A	p.Gly417Ser	missense_variant	11/28	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.1249G>A	p.Gly417Ser	missense_variant	11/28	1	NM_001141980.3	ENSP00000371475	P4	Q12888-2

Frequencies

GnomAD3 genomes

AF:

0.282

AC:

42769

AN:

151868

Hom.:

10211

Cov.:

show subpopulations

Gnomad AFR

AF:

0.650

Gnomad AMI

AF:

0.107

Gnomad AMR

AF:

0.215

Gnomad ASJ

AF:

0.186

Gnomad EAS

AF:

0.397

Gnomad SAS

AF:

0.236

Gnomad FIN

AF:

0.0864

Gnomad MID

AF:

0.194

Gnomad NFE

AF:

0.107

Gnomad OTH

AF:

0.236

GnomAD3 exomes

AF:

0.199

AC:

49938

AN:

251248

Hom.:

7832

AF XY:

0.188

AC XY:

25582

AN XY:

135796

show subpopulations

Gnomad AFR exome

AF:

0.657

Gnomad AMR exome

AF:

0.215

Gnomad ASJ exome

AF:

0.195

Gnomad EAS exome

AF:

0.411

Gnomad SAS exome

AF:

0.225

Gnomad FIN exome

AF:

0.0817

Gnomad NFE exome

AF:

0.112

Gnomad OTH exome

AF:

0.153

GnomAD4 exome

AF:

0.143

AC:

209332

AN:

1461404

Hom.:

22766

Cov.:

AF XY:

0.144

AC XY:

104445

AN XY:

727016

show subpopulations

Gnomad4 AFR exome

AF:

0.670

Gnomad4 AMR exome

AF:

0.212

Gnomad4 ASJ exome

AF:

0.194

Gnomad4 EAS exome

AF:

0.407

Gnomad4 SAS exome

AF:

0.218

Gnomad4 FIN exome

AF:

0.0822

Gnomad4 NFE exome

AF:

0.109

Gnomad4 OTH exome

AF:

0.176

GnomAD4 genome

AF:

0.282

AC:

42869

AN:

151986

Hom.:

10247

Cov.:

AF XY:

0.279

AC XY:

20700

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.650

Gnomad4 AMR

AF:

0.215

Gnomad4 ASJ

AF:

0.186

Gnomad4 EAS

AF:

0.397

Gnomad4 SAS

AF:

0.236

Gnomad4 FIN

AF:

0.0864

Gnomad4 NFE

AF:

0.107

Gnomad4 OTH

AF:

0.240

Alfa

AF:

0.151

Hom.:

7286

Bravo

AF:

0.311

TwinsUK

AF:

0.103

AC:

383

ALSPAC

AF:

0.119

AC:

459

ESP6500AA

AF:

0.630

AC:

2774

ESP6500EA

AF:

0.113

AC:

971

ExAC

AF:

0.206

AC:

25011

Asia WGS

AF:

0.342

AC:

1186

AN:

3478

EpiCase

AF:

0.120

EpiControl

AF:

0.121

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.061

.;T;T;.;T

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.66

T;T;T;T;T

MetaRNN

Benign

0.0000073

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.69

.;N;.;.;.

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.27

PROVEAN

Benign

0.59

N;N;N;N;N

REVEL

Benign

0.074

Sift

Benign

0.049

D;D;D;D;T

Sift4G

Benign

0.46

T;T;T;T;.

Polyphen

0.0

B;B;.;.;.

Vest4

0.042

MPC

0.066

ClinPred

0.019

GERP RS

5.3

Varity_R

0.070

gMVP

0.24

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