rs2242069

Positions:

• chr15-43421436-A-C

Variant summary

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

The NM_001141980.3(TP53BP1):​c.4101-262T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 152,036 control chromosomes in the GnomAD database, including 11,489 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 0.32 (11489 hom., cov: 32)
• Consequence: TP53BP1 NM_001141980.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.939

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TP53BP1	NM_001141980.3	c.4101-262T>G		intron_variant		ENST00000382044.9	NP_001135452.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TP53BP1	ENST00000382044.9	c.4101-262T>G		intron_variant		1	NM_001141980.3	ENSP00000371475.5

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48561 AN: 151918 Hom.: 11454 Cov.: 32

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.320 AC: 48661 AN: 152036 Hom.: 11489 Cov.: 32 AF XY: 0.315 AC XY: 23454 AN XY: 74348

Gnomad4 AFR AF: 0.668

Gnomad4 AMR AF: 0.252

Gnomad4 ASJ AF: 0.229

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.278

Alfa AF: 0.201 Hom.: 2692

Bravo AF: 0.348

Asia WGS AF: 0.356 AC: 1236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	11
DANN	Benign	0.70

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: rs2242069; hg19: chr15-43713634;