rs2444030

Variant names:

• chr15-43449558-C-G
• rs2444030
• NM_001141980.3:c.2717-2073G>C

Your query was ambiguous. Multiple possible variants found:

• chr15-43449558-C-G
• chr15-43449558-C-T

Variant summary

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

The NM_001141980.3(TP53BP1):​c.2717-2073G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.98 in 152,314 control chromosomes in the GnomAD database, including 73,233 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 0.98 (73233 hom., cov: 31)
• Consequence: TP53BP1 NM_001141980.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.125
• Publications: 3 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.988 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.2717-2073G>C		intron	N/A	NP_001135452.1
	TP53BP1	NM_001141979.3		c.2717-2073G>C		intron	N/A	NP_001135451.1
	TP53BP1	NM_005657.4		c.2702-2073G>C		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.2717-2073G>C		intron	N/A	ENSP00000371475.5
	TP53BP1	ENST00000450115.6	TSL:1	c.2717-2073G>C		intron	N/A	ENSP00000393497.2
	TP53BP1	ENST00000263801.7	TSL:1	c.2702-2073G>C		intron	N/A	ENSP00000263801.3

Frequencies

GnomAD3 genomes AF: 0.980 AC: 149219 AN: 152196 Hom.: 73173 Cov.: 31

Gnomad AFR AF: 0.996

Gnomad AMI AF: 0.996

Gnomad AMR AF: 0.991

Gnomad ASJ AF: 0.997

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.997

Gnomad FIN AF: 0.936

Gnomad MID AF: 0.997

Gnomad NFE AF: 0.972

Gnomad OTH AF: 0.986

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

GnomAD4 genome AF: 0.980 AC: 149338 AN: 152314 Hom.: 73233 Cov.: 31 AF XY: 0.979 AC XY: 72916 AN XY: 74472

African (AFR) AF: 0.996 AC: 41382 AN: 41562

American (AMR) AF: 0.991 AC: 15172 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.997 AC: 3462 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5190 AN: 5190

South Asian (SAS) AF: 0.997 AC: 4815 AN: 4828

European-Finnish (FIN) AF: 0.936 AC: 9929 AN: 10608

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 0.972 AC: 66105 AN: 68030

Other (OTH) AF: 0.986 AC: 2082 AN: 2112

Alfa AF: 0.973 Hom.: 8380

Bravo AF: 0.985

Asia WGS AF: 0.998 AC: 3471 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.1
DANN	Benign	0.37
PhyloP100		-0.13
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: rs2444030; hg19: chr15-43741756;