rs2242069

Variant names:

• chr15-43421436-A-C
• rs2242069
• NM_001141980.3:c.4101-262T>G

Variant summary

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

The NM_001141980.3(TP53BP1):​c.4101-262T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 152,036 control chromosomes in the GnomAD database, including 11,489 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 0.32 (11489 hom., cov: 32)
• Consequence: TP53BP1 NM_001141980.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.939
• Publications: 22 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 = 0.661 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TP53BP1	NM_001141980.3	MANE Select	c.4101-262T>G		intron	N/A	NP_001135452.1
	TP53BP1	NM_001141979.3		c.4101-262T>G		intron	N/A	NP_001135451.1
	TP53BP1	NM_005657.4		c.4086-262T>G		intron	N/A	NP_005648.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TP53BP1	ENST00000382044.9	TSL:1 MANE Select	c.4101-262T>G		intron	N/A	ENSP00000371475.5
	TP53BP1	ENST00000450115.6	TSL:1	c.4101-262T>G		intron	N/A	ENSP00000393497.2
	TP53BP1	ENST00000263801.7	TSL:1	c.4086-262T>G		intron	N/A	ENSP00000263801.3

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48561 AN: 151918 Hom.: 11454 Cov.: 32

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.320 AC: 48661 AN: 152036 Hom.: 11489 Cov.: 32 AF XY: 0.315 AC XY: 23454 AN XY: 74348

African (AFR) AF: 0.668 AC: 27656 AN: 41432

American (AMR) AF: 0.252 AC: 3847 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 795 AN: 3470

East Asian (EAS) AF: 0.398 AC: 2048 AN: 5150

South Asian (SAS) AF: 0.259 AC: 1250 AN: 4818

European-Finnish (FIN) AF: 0.127 AC: 1341 AN: 10600

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10903 AN: 67974

Other (OTH) AF: 0.278 AC: 588 AN: 2112

Alfa AF: 0.207 Hom.: 4769

Bravo AF: 0.348

Asia WGS AF: 0.356 AC: 1236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	11
DANN	Benign	0.70
PhyloP100		-0.94
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: rs2242069; hg19: chr15-43713634;