rs689754

Positions:

• chr15-43483697-A-G

Variant summary

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

The NM_001141980.3(TP53BP1):​c.372-2675T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,226 control chromosomes in the GnomAD database, including 8,104 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 0.25 (8104 hom., cov: 32)
• Consequence: TP53BP1 NM_001141980.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.285

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TP53BP1	NM_001141980.3	c.372-2675T>C		intron_variant		ENST00000382044.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TP53BP1	ENST00000382044.9	c.372-2675T>C		intron_variant		1	NM_001141980.3	P4

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38334 AN: 152108 Hom.: 8084 Cov.: 32

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.0464

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.252 AC: 38410 AN: 152226 Hom.: 8104 Cov.: 32 AF XY: 0.248 AC XY: 18450 AN XY: 74434

Gnomad4 AFR AF: 0.575

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.359

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.0464

Gnomad4 NFE AF: 0.100

Gnomad4 OTH AF: 0.212

Alfa AF: 0.145 Hom.: 900

Bravo AF: 0.282

Asia WGS AF: 0.297 AC: 1033 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.3
DANN	Benign	0.41

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: rs689754; hg19: chr15-43775895;