rs17884607

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_000546.6(TP53):c.672+48G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000514 in 1,555,924 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 (★★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

TP53
NM_000546.6 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.241

Publications

3 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

TP53 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 17-7674811-C-A is Benign according to our data. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-A is described in CliVar as Likely_benign. Clinvar id is 1326387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TP53	NM_000546.6 link	c.672+48G>T		intron_variant	Intron 6 of 10	ENST00000269305.9	NP_000537.3	P04637-1K7PPA8Q53GA5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TP53	ENST00000269305.9 link	c.672+48G>T		intron_variant	Intron 6 of 10	1	NM_000546.6	ENSP00000269305.4		P04637-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000421

AC:

AN:

237332

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000941

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000285

AC:

AN:

1403594

Hom.:

Cov.:

AF XY:

0.00000571

AC XY:

AN XY:

700864

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32092

American (AMR)

AF:

0.00

AC:

AN:

43460

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25642

East Asian (EAS)

AF:

0.00

AC:

AN:

39072

South Asian (SAS)

AF:

0.00

AC:

AN:

84324

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53014

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5650

European-Non Finnish (NFE)

AF:

0.00000188

AC:

AN:

1061930

Other (OTH)

AF:

0.0000342

AC:

AN:

58410

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41568

American (AMR)

AF:

0.00

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000207

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000227

ClinVar

Significance: Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 19, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 28664506) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Li-Fraumeni syndrome 1

Benign:1

Jun 18, 2022

Genome-Nilou Lab

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Li-Fraumeni syndrome

Benign:1

Aug 04, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary cancer-predisposing syndrome

Benign:1

Jun 18, 2022

Genome-Nilou Lab

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

-0.78

CADD

Benign

2.3

(source)

DANN

Benign

0.82

PhyloP100

-0.24

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over