1-223783043-T-G

Variant names:

• chr1-223783043-T-G
• rs1153942
• NM_001031685.3:c.3363+1072A>C

Variant summary

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

The NM_001031685.3(TP53BP2):​c.3363+1072A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.891 in 152,194 control chromosomes in the GnomAD database, including 60,625 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 0.89 (60625 hom., cov: 31)
• Consequence: TP53BP2 NM_001031685.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 9 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TP53BP2	NM_001031685.3	c.3363+1072A>C		intron_variant	Intron 17 of 17	ENST00000343537.12	NP_001026855.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TP53BP2	ENST00000343537.12	c.3363+1072A>C		intron_variant	Intron 17 of 17	1	NM_001031685.3	ENSP00000341957.7
TP53BP2	ENST00000391878.6	c.2976+1072A>C		intron_variant	Intron 18 of 18	1		ENSP00000375750.2
TP53BP2	ENST00000483398.5	n.*1397+1072A>C		intron_variant	Intron 7 of 7	2		ENSP00000417174.1
TP53BP2	ENST00000498843.5	n.2675+1072A>C		intron_variant	Intron 10 of 10	2

Frequencies

GnomAD3 genomes AF: 0.891 AC: 135454 AN: 152076 Hom.: 60573 Cov.: 31

Gnomad AFR AF: 0.971

Gnomad AMI AF: 0.833

Gnomad AMR AF: 0.887

Gnomad ASJ AF: 0.881

Gnomad EAS AF: 0.784

Gnomad SAS AF: 0.772

Gnomad FIN AF: 0.849

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.866

Gnomad OTH AF: 0.899

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

GnomAD4 genome AF: 0.891 AC: 135563 AN: 152194 Hom.: 60625 Cov.: 31 AF XY: 0.886 AC XY: 65910 AN XY: 74408

African (AFR) AF: 0.971 AC: 40350 AN: 41554

American (AMR) AF: 0.887 AC: 13571 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.881 AC: 3059 AN: 3472

East Asian (EAS) AF: 0.782 AC: 4033 AN: 5154

South Asian (SAS) AF: 0.773 AC: 3718 AN: 4812

European-Finnish (FIN) AF: 0.849 AC: 9003 AN: 10602

Middle Eastern (MID) AF: 0.895 AC: 263 AN: 294

European-Non Finnish (NFE) AF: 0.866 AC: 58911 AN: 67994

Other (OTH) AF: 0.899 AC: 1895 AN: 2108

Alfa AF: 0.875 Hom.: 138524

Bravo AF: 0.898

Asia WGS AF: 0.807 AC: 2810 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.022
DANN	Benign	0.52
PhyloP100		-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: rs1153942; hg19: chr1-223970745;