15-43487488-C-T

Variant names:

• chr15-43487488-C-T
• rs2439832
• NM_001141980.3:c.371+4181G>A

Variant summary

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

The NM_001141980.3(TP53BP1):​c.371+4181G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 151,954 control chromosomes in the GnomAD database, including 10,208 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 0.28 (10208 hom., cov: 31)
• Consequence: TP53BP1 NM_001141980.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0960

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TP53BP1	NM_001141980.3	c.371+4181G>A		intron_variant	Intron 4 of 27	ENST00000382044.9	NP_001135452.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TP53BP1	ENST00000382044.9	c.371+4181G>A		intron_variant	Intron 4 of 27	1	NM_001141980.3	ENSP00000371475.5

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42519 AN: 151836 Hom.: 10172 Cov.: 31

Gnomad AFR AF: 0.650

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.0865

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.280 AC: 42619 AN: 151954 Hom.: 10208 Cov.: 31 AF XY: 0.277 AC XY: 20585 AN XY: 74300

Gnomad4 AFR AF: 0.650

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.397

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.0865

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.235

Alfa AF: 0.208 Hom.: 1071

Bravo AF: 0.309

Asia WGS AF: 0.343 AC: 1191 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.1
DANN	Benign	0.31

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: rs2439832; hg19: chr15-43779686;