rs17782975

Positions:

• chr15-43505841-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005657.4(TP53BP1):​c.-9+4529A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0556 in 152,342 control chromosomes in the GnomAD database, including 346 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 0.056 (346 hom., cov: 32)
• Consequence: TP53BP1 NM_005657.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.667

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.082 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TP53BP1	NM_005657.4	c.-9+4529A>G		intron_variant			NP_005648.1
TP53BP1	NM_001411050.1	c.-215+4529A>G		intron_variant			NP_001397979.1
TP53BP1	XM_047432994.1	c.-215+4529A>G		intron_variant			XP_047288950.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TP53BP1	ENST00000263801.7	c.-9+4529A>G		intron_variant		1		ENSP00000263801.3
TP53BP1	ENST00000477089.1	n.359+4529A>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0557 AC: 8478 AN: 152224 Hom.: 346 Cov.: 32

Gnomad AFR AF: 0.0165

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.0661

Gnomad ASJ AF: 0.0853

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0164

Gnomad FIN AF: 0.0437

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0839

Gnomad OTH AF: 0.0645

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0556 AC: 8472 AN: 152342 Hom.: 346 Cov.: 32 AF XY: 0.0521 AC XY: 3883 AN XY: 74502

Gnomad4 AFR AF: 0.0164

Gnomad4 AMR AF: 0.0658

Gnomad4 ASJ AF: 0.0853

Gnomad4 EAS AF: 0.000192

Gnomad4 SAS AF: 0.0170

Gnomad4 FIN AF: 0.0437

Gnomad4 NFE AF: 0.0839

Gnomad4 OTH AF: 0.0638

Alfa AF: 0.0796 Hom.: 751

Bravo AF: 0.0565

Asia WGS AF: 0.0120 AC: 40 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	13
DANN	Benign	0.85

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

Other links and lift over

dbSNP: rs17782975; hg19: chr15-43798039;