rs113302588

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000546.6(TP53):​c.783-33T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000127 in 1,587,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.00047 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000091 ( 0 hom. )

Consequence

TP53
NM_000546.6 intron

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.653

Publications

2 publications found
Variant links:
Genes affected
TP53 (HGNC:11998): (tumor protein p53) This gene encodes a tumor suppressor protein containing transcriptional activation, DNA binding, and oligomerization domains. The encoded protein responds to diverse cellular stresses to regulate expression of target genes, thereby inducing cell cycle arrest, apoptosis, senescence, DNA repair, or changes in metabolism. Mutations in this gene are associated with a variety of human cancers, including hereditary cancers such as Li-Fraumeni syndrome. Alternative splicing of this gene and the use of alternate promoters result in multiple transcript variants and isoforms. Additional isoforms have also been shown to result from the use of alternate translation initiation codons from identical transcript variants (PMIDs: 12032546, 20937277). [provided by RefSeq, Dec 2016]
TP53 Gene-Disease associations (from GenCC):
  • breast cancer
    Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
  • Li-Fraumeni syndrome
    Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet
  • Li-Fraumeni syndrome 1
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Genomics England PanelApp
  • adrenocortical carcinoma, hereditary
    Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
  • sarcoma
    Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
  • bone marrow failure syndrome 5
    Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
  • colorectal cancer
    Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
  • choroid plexus carcinoma
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4
This position, referring to a specific DNA site, is a probable branch point but rather VUS (scored 4 / 10). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 17-7673870-A-G is Benign according to our data. Variant chr17-7673870-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 492614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000466 (71/152286) while in subpopulation AFR AF = 0.00156 (65/41576). AF 95% confidence interval is 0.00126. There are 0 homozygotes in GnomAd4. There are 32 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
BS2
High AC in GnomAd4 at 71 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TP53NM_000546.6 linkc.783-33T>C intron_variant Intron 7 of 10 ENST00000269305.9 NP_000537.3 P04637-1K7PPA8Q53GA5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TP53ENST00000269305.9 linkc.783-33T>C intron_variant Intron 7 of 10 1 NM_000546.6 ENSP00000269305.4 P04637-1

Frequencies

GnomAD3 genomes
AF:
0.000460
AC:
70
AN:
152168
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00154
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000328
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000478
GnomAD2 exomes
AF:
0.000155
AC:
31
AN:
200158
AF XY:
0.0000933
show subpopulations
Gnomad AFR exome
AF:
0.00169
Gnomad AMR exome
AF:
0.000248
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000117
Gnomad OTH exome
AF:
0.000189
GnomAD4 exome
AF:
0.0000906
AC:
130
AN:
1435314
Hom.:
0
Cov.:
33
AF XY:
0.0000745
AC XY:
53
AN XY:
711778
show subpopulations
African (AFR)
AF:
0.00244
AC:
80
AN:
32844
American (AMR)
AF:
0.000277
AC:
11
AN:
39640
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25632
East Asian (EAS)
AF:
0.00
AC:
0
AN:
38320
South Asian (SAS)
AF:
0.0000480
AC:
4
AN:
83352
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52014
Middle Eastern (MID)
AF:
0.000184
AC:
1
AN:
5446
European-Non Finnish (NFE)
AF:
0.00000546
AC:
6
AN:
1098592
Other (OTH)
AF:
0.000471
AC:
28
AN:
59474
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.477
Heterozygous variant carriers
0
8
16
24
32
40
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
4
8
12
16
20
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.000466
AC:
71
AN:
152286
Hom.:
0
Cov.:
31
AF XY:
0.000430
AC XY:
32
AN XY:
74472
show subpopulations
African (AFR)
AF:
0.00156
AC:
65
AN:
41576
American (AMR)
AF:
0.000327
AC:
5
AN:
15278
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5174
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4828
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10618
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68024
Other (OTH)
AF:
0.000473
AC:
1
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.484
Heterozygous variant carriers
0
3
7
10
14
17
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.000217
Hom.:
0
Bravo
AF:
0.000582
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Li-Fraumeni syndrome 1 Benign:2
Jul 07, 2023
KCCC/NGS Laboratory, Kuwait Cancer Control Center
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Jun 18, 2022
Genome-Nilou Lab
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Hereditary cancer-predisposing syndrome Benign:2
Nov 17, 2015
Color Diagnostics, LLC DBA Color Health
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Jun 18, 2022
Genome-Nilou Lab
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

not specified Benign:1
Mar 04, 2025
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Hereditary breast ovarian cancer syndrome Benign:1
Apr 19, 2022
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Squamous cell carcinoma of the head and neck Benign:1
May 28, 2019
Mendelics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
6.1
DANN
Benign
0.47
PhyloP100
0.65
BranchPoint Hunter
4.0
PromoterAI
-0.0092
Neutral
Mutation Taster
=100/0
polymorphism

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

Other links and lift over

dbSNP: rs113302588; hg19: chr17-7577188; API