15-43487488-C-T

Variant names:

• chr15-43487488-C-T
• rs2439832
• NM_001141980.3:c.371+4181G>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.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
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001141980.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TP53BP1	NM_001141980.3	MANE Select	c.371+4181G>A		intron	N/A	NP_001135452.1	Q12888-2
	TP53BP1	NM_001141979.3		c.371+4181G>A		intron	N/A	NP_001135451.1	Q12888-3
	TP53BP1	NM_005657.4		c.356+4181G>A		intron	N/A	NP_005648.1	Q12888-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TP53BP1	ENST00000382044.9	TSL:1 MANE Select	c.371+4181G>A		intron	N/A	ENSP00000371475.5	Q12888-2
	TP53BP1	ENST00000450115.6	TSL:1	c.371+4181G>A		intron	N/A	ENSP00000393497.2	Q12888-3
	TP53BP1	ENST00000263801.7	TSL:1	c.356+4181G>A		intron	N/A	ENSP00000263801.3	Q12888-1

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

African (AFR) AF: 0.650 AC: 26909 AN: 41400

American (AMR) AF: 0.212 AC: 3228 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 640 AN: 3472

East Asian (EAS) AF: 0.397 AC: 2055 AN: 5176

South Asian (SAS) AF: 0.236 AC: 1133 AN: 4808

European-Finnish (FIN) AF: 0.0865 AC: 915 AN: 10572

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7085 AN: 67960

Other (OTH) AF: 0.235 AC: 496 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.1
DANN	Benign	0.31
PhyloP100		0.096
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: rs2439832; hg19: chr15-43779686;