rs12723025

Variant names:

• chr1-223789817-T-C
• rs12723025
• NM_001031685.3:c.2997-643A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.87).
• 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 rank	MANE	Protein	UniProt
TP53BP2	NM_001031685.3	c.2997-643A>G		intron_variant	Intron 15 of 17	ENST00000343537.12	NP_001026855.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TP53BP2	ENST00000343537.12	c.2997-643A>G		intron_variant	Intron 15 of 17	1	NM_001031685.3	ENSP00000341957.7
TP53BP2	ENST00000391878.6	c.2610-643A>G		intron_variant	Intron 16 of 18	1		ENSP00000375750.2
TP53BP2	ENST00000483398.5	n.*1031-643A>G		intron_variant	Intron 5 of 7	2		ENSP00000417174.1
TP53BP2	ENST00000498843.5	n.2309-643A>G		intron_variant	Intron 8 of 10	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

African (AFR) AF: 0.0154 AC: 640 AN: 41554

American (AMR) AF: 0.0694 AC: 1061 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0864 AC: 300 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.0155 AC: 75 AN: 4824

European-Finnish (FIN) AF: 0.119 AC: 1263 AN: 10584

Middle Eastern (MID) AF: 0.175 AC: 51 AN: 292

European-Non Finnish (NFE) AF: 0.0816 AC: 5551 AN: 67990

Other (OTH) AF: 0.0729 AC: 154 AN: 2112

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
PhyloP100		-0.070
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: rs12723025; hg19: chr1-223977519;