15-43483534-A-T

Variant names:

• chr15-43483534-A-T
• rs544122
• NM_001141980.3:c.372-2512T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001141980.3(TP53BP1):​c.372-2512T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,084 control chromosomes in the GnomAD database, including 5,240 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 0.21 (5240 hom., cov: 32)
• Consequence: TP53BP1 NM_001141980.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.474
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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 = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TP53BP1	NM_001141980.3	c.372-2512T>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.372-2512T>A		intron_variant	Intron 4 of 27	1	NM_001141980.3	ENSP00000371475.5

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32249 AN: 151966 Hom.: 5229 Cov.: 32

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.0463

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.0993

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.212 AC: 32308 AN: 152084 Hom.: 5240 Cov.: 32 AF XY: 0.209 AC XY: 15565 AN XY: 74352

African (AFR) AF: 0.452 AC: 18748 AN: 41438

American (AMR) AF: 0.184 AC: 2805 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 622 AN: 3470

East Asian (EAS) AF: 0.260 AC: 1348 AN: 5176

South Asian (SAS) AF: 0.209 AC: 1007 AN: 4822

European-Finnish (FIN) AF: 0.0463 AC: 491 AN: 10598

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.0993 AC: 6748 AN: 67988

Other (OTH) AF: 0.186 AC: 393 AN: 2114

Alfa AF: 0.0649 Hom.: 113

Bravo AF: 0.237

Asia WGS AF: 0.240 AC: 833 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	3.4
DANN	Benign	0.53
PhyloP100		0.47
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs544122; hg19: chr15-43775732;