rs689754

Variant names:

• chr15-43483697-A-G
• rs689754
• NM_001141980.3:c.372-2675T>C

Variant summary

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

The NM_001141980.3(TP53BP1):​c.372-2675T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,226 control chromosomes in the GnomAD database, including 8,104 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 0.25 (8104 hom., cov: 32)
• Consequence: TP53BP1 NM_001141980.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.285
• Publications: 10 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.569 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.372-2675T>C		intron	N/A	NP_001135452.1	Q12888-2
	TP53BP1	NM_001141979.3		c.372-2675T>C		intron	N/A	NP_001135451.1	Q12888-3
	TP53BP1	NM_005657.4		c.357-2675T>C		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.372-2675T>C		intron	N/A	ENSP00000371475.5	Q12888-2
	TP53BP1	ENST00000450115.6	TSL:1	c.372-2675T>C		intron	N/A	ENSP00000393497.2	Q12888-3
	TP53BP1	ENST00000263801.7	TSL:1	c.357-2675T>C		intron	N/A	ENSP00000263801.3	Q12888-1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38334 AN: 152108 Hom.: 8084 Cov.: 32

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.0464

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.252 AC: 38410 AN: 152226 Hom.: 8104 Cov.: 32 AF XY: 0.248 AC XY: 18450 AN XY: 74434

African (AFR) AF: 0.575 AC: 23844 AN: 41480

American (AMR) AF: 0.201 AC: 3071 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 629 AN: 3472

East Asian (EAS) AF: 0.359 AC: 1860 AN: 5188

South Asian (SAS) AF: 0.228 AC: 1102 AN: 4828

European-Finnish (FIN) AF: 0.0464 AC: 493 AN: 10620

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.100 AC: 6813 AN: 68018

Other (OTH) AF: 0.212 AC: 448 AN: 2114

Alfa AF: 0.133 Hom.: 1165

Bravo AF: 0.282

Asia WGS AF: 0.297 AC: 1033 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.3
DANN	Benign	0.41
PhyloP100		-0.28
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: rs689754; hg19: chr15-43775895;