rs17880172

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000546.6(TP53):​c.782+17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0003 in 1,560,724 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0017 ( 1 hom., cov: 31)
Exomes 𝑓: 0.00015 ( 1 hom. )

Consequence

TP53
NM_000546.6 intron

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.569
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 17-7674164-G-A is Benign according to our data. Variant chr17-7674164-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 137692.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 = 0.00167 (254/152120) while in subpopulation AFR AF= 0.00592 (246/41528). AF 95% confidence interval is 0.00532. There are 1 homozygotes in gnomad4. There are 117 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAd4 at 254 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TP53NM_000546.6 linkc.782+17C>T 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.782+17C>T intron_variant Intron 7 of 10 1 NM_000546.6 ENSP00000269305.4 P04637-1

Frequencies

GnomAD3 genomes
AF:
0.00167
AC:
254
AN:
152002
Hom.:
1
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00594
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:
0.0000147
Gnomad OTH
AF:
0.000957
GnomAD3 exomes
AF:
0.000430
AC:
108
AN:
251242
Hom.:
2
AF XY:
0.000287
AC XY:
39
AN XY:
135794
show subpopulations
Gnomad AFR exome
AF:
0.00585
Gnomad AMR exome
AF:
0.000318
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000152
AC:
214
AN:
1408604
Hom.:
1
Cov.:
29
AF XY:
0.000134
AC XY:
94
AN XY:
703956
show subpopulations
Gnomad4 AFR exome
AF:
0.00522
Gnomad4 AMR exome
AF:
0.000314
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000470
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.40e-7
Gnomad4 OTH exome
AF:
0.000409
GnomAD4 genome
AF:
0.00167
AC:
254
AN:
152120
Hom.:
1
Cov.:
31
AF XY:
0.00157
AC XY:
117
AN XY:
74374
show subpopulations
Gnomad4 AFR
AF:
0.00592
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000947
Alfa
AF:
0.000555
Hom.:
0
Bravo
AF:
0.00157

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:11
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Hereditary cancer-predisposing syndrome Benign:4
Jul 21, 2015
Color Diagnostics, LLC DBA Color Health
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Jul 12, 2017
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.
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

- -

Nov 18, 2014
Ambry Genetics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Li-Fraumeni syndrome 1 Benign:2
Feb 01, 2025
KCCC/NGS Laboratory, Kuwait Cancer Control Center
Significance: 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:2
Jun 07, 2017
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Jan 03, 2014
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Li-Fraumeni syndrome Benign:1
Feb 04, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Breast and/or ovarian cancer Benign:1
Jan 12, 2023
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Significance: Likely 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

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
0.27
DANN
Benign
0.33
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs17880172; hg19: chr17-7577482; COSMIC: COSV53533660; COSMIC: COSV53533660; API