1-223780251-C-T

Position:

• chr1-223780251-C-T

Variant summary

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

The NM_001031685.3(TP53BP2):​c.*602G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 152,110 control chromosomes in the GnomAD database, including 10,500 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 0.31 (10500 hom., cov: 33)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: TP53BP2 NM_001031685.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TP53BP2	NM_001031685.3	c.*602G>A		3_prime_UTR_variant	18/18	ENST00000343537.12	NP_001026855.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TP53BP2	ENST00000343537	c.*602G>A		3_prime_UTR_variant	18/18	1	NM_001031685.3	ENSP00000341957.7
TP53BP2	ENST00000391878	c.*602G>A		3_prime_UTR_variant	19/19	1		ENSP00000375750.2

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46645 AN: 151984 Hom.: 10473 Cov.: 33

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.290

GnomAD4 exome AF: 0.250 AC: 2 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 NFE exome AF: 0.250

GnomAD4 genome AF: 0.307 AC: 46732 AN: 152102 Hom.: 10500 Cov.: 33 AF XY: 0.303 AC XY: 22497 AN XY: 74360

Gnomad4 AFR AF: 0.637

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.292

Alfa AF: 0.189 Hom.: 3284

Bravo AF: 0.336

Asia WGS AF: 0.268 AC: 932 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.0
DANN	Benign	0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs17739; hg19: chr1-223967953;