chr1-223780251-C-T

Variant names:

• chr1-223780251-C-T
• rs17739
• NM_001031685.3:c.*602G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 20 publications found

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]

TP53BP2 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031685.3. 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
	TP53BP2	NM_001031685.3	MANE Select	c.*602G>A		3_prime_UTR	Exon 18 of 18	NP_001026855.2
	TP53BP2	NM_005426.3		c.*602G>A		3_prime_UTR	Exon 19 of 19	NP_005417.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TP53BP2	ENST00000343537.12	TSL:1 MANE Select	c.*602G>A		3_prime_UTR	Exon 18 of 18	ENSP00000341957.7
	TP53BP2	ENST00000391878.6	TSL:1	c.*602G>A		3_prime_UTR	Exon 19 of 19	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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 2 AN: 8

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.637 AC: 26442 AN: 41494

American (AMR) AF: 0.273 AC: 4175 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 645 AN: 3468

East Asian (EAS) AF: 0.332 AC: 1717 AN: 5172

South Asian (SAS) AF: 0.150 AC: 725 AN: 4822

European-Finnish (FIN) AF: 0.131 AC: 1379 AN: 10562

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10868 AN: 67984

Other (OTH) AF: 0.292 AC: 617 AN: 2110

Alfa AF: 0.208 Hom.: 5572

Bravo AF: 0.336

Asia WGS AF: 0.268 AC: 932 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.0
DANN	Benign	0.47
PhyloP100		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs17739; hg19: chr1-223967953;