rs12723025

Positions:

• chr1-223789817-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001031685.3(TP53BP2):​c.2997-643A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0599 in 152,208 control chromosomes in the GnomAD database, including 390 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 0.060 (390 hom., cov: 32)
• Consequence: TP53BP2 NM_001031685.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700

Genes affected

TP53BP2 (HGNC:12000): (tumor protein p53 binding protein 2) This gene encodes a member of the ASPP (apoptosis-stimulating protein of p53) family of p53 interacting proteins. The protein contains four ankyrin repeats and an SH3 domain involved in protein-protein interactions. It is localized to the perinuclear region of the cytoplasm, and regulates apoptosis and cell growth through interactions with other regulatory molecules including members of the p53 family. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TP53BP2	NM_001031685.3	c.2997-643A>G		intron_variant		ENST00000343537.12	NP_001026855.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TP53BP2	ENST00000343537.12	c.2997-643A>G		intron_variant		1	NM_001031685.3	ENSP00000341957	P1
TP53BP2	ENST00000391878.6	c.2610-643A>G		intron_variant		1		ENSP00000375750
TP53BP2	ENST00000483398.5	c.*1031-643A>G		intron_variant, NMD_transcript_variant		2		ENSP00000417174
TP53BP2	ENST00000498843.5	n.2309-643A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0600 AC: 9132 AN: 152090 Hom.: 391 Cov.: 32

Gnomad AFR AF: 0.0154

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0696

Gnomad ASJ AF: 0.0864

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0153

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.0816

Gnomad OTH AF: 0.0742

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

GnomAD4 genome AF: 0.0599 AC: 9120 AN: 152208 Hom.: 390 Cov.: 32 AF XY: 0.0593 AC XY: 4415 AN XY: 74420

Gnomad4 AFR AF: 0.0154

Gnomad4 AMR AF: 0.0694

Gnomad4 ASJ AF: 0.0864

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0155

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.0816

Gnomad4 OTH AF: 0.0729

Alfa AF: 0.0665 Hom.: 68

Bravo AF: 0.0558

Asia WGS AF: 0.0120 AC: 41 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.8
DANN	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs12723025; hg19: chr1-223977519;