rs2444030

Positions:

• chr15-43449558-C-G
• chr15-43449558-C-T

Variant summary

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

The NM_001141980.3(TP53BP1):​c.2717-2073G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.98 in 152,314 control chromosomes in the GnomAD database, including 73,233 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 0.98 (73233 hom., cov: 31)
• Consequence: TP53BP1 NM_001141980.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.125

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.988 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TP53BP1	NM_001141980.3	c.2717-2073G>C		intron_variant		ENST00000382044.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TP53BP1	ENST00000382044.9	c.2717-2073G>C		intron_variant		1	NM_001141980.3	P4

Frequencies

GnomAD3 genomes AF: 0.980 AC: 149219 AN: 152196 Hom.: 73173 Cov.: 31

Gnomad AFR AF: 0.996

Gnomad AMI AF: 0.996

Gnomad AMR AF: 0.991

Gnomad ASJ AF: 0.997

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.997

Gnomad FIN AF: 0.936

Gnomad MID AF: 0.997

Gnomad NFE AF: 0.972

Gnomad OTH AF: 0.986

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

GnomAD4 genome AF: 0.980 AC: 149338 AN: 152314 Hom.: 73233 Cov.: 31 AF XY: 0.979 AC XY: 72916 AN XY: 74472

Gnomad4 AFR AF: 0.996

Gnomad4 AMR AF: 0.991

Gnomad4 ASJ AF: 0.997

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.997

Gnomad4 FIN AF: 0.936

Gnomad4 NFE AF: 0.972

Gnomad4 OTH AF: 0.986

Alfa AF: 0.973 Hom.: 8380

Bravo AF: 0.985

Asia WGS AF: 0.998 AC: 3471 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.1
DANN	Benign	0.37

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: rs2444030; hg19: chr15-43741756;