17-7676301-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000546.6(TP53):c.97-29C>A 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 1,613,888 control chromosomes in the GnomAD database, including 3,281 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.072 ( 478 hom., cov: 31)

Exomes 𝑓: 0.059 ( 2803 hom. )

Consequence

TP53
NM_000546.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 0.207

Publications

39 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 17-7676301-G-T is Benign according to our data. Variant chr17-7676301-G-T is described in ClinVar as Benign. ClinVar VariationId is 256604.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TP53	NM_000546.6 link	c.97-29C>A		intron_variant	Intron 3 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.97-29C>A		intron_variant	Intron 3 of 10	1	NM_000546.6	ENSP00000269305.4		P04637-1

Frequencies

GnomAD3 genomes

AF:

0.0718

AC:

10921

AN:

151998

Hom.:

474

Cov.:

show subpopulations

Gnomad AFR

AF:

0.103

Gnomad AMI

AF:

0.106

Gnomad AMR

AF:

0.0527

Gnomad ASJ

AF:

0.0495

Gnomad EAS

AF:

0.0696

Gnomad SAS

AF:

0.0623

Gnomad FIN

AF:

0.106

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0541

Gnomad OTH

AF:

0.0543

GnomAD2 exomes

AF:

0.0651

AC:

16343

AN:

251016

AF XY:

0.0640

show subpopulations

Gnomad AFR exome

AF:

0.108

Gnomad AMR exome

AF:

0.0534

Gnomad ASJ exome

AF:

0.0469

Gnomad EAS exome

AF:

0.0677

Gnomad FIN exome

AF:

0.108

Gnomad NFE exome

AF:

0.0545

Gnomad OTH exome

AF:

0.0597

GnomAD4 exome

AF:

0.0587

AC:

85744

AN:

1461772

Hom.:

2803

Cov.:

AF XY:

0.0587

AC XY:

42655

AN XY:

727192

show subpopulations

African (AFR)

AF:

0.103

AC:

3458

AN:

33476

American (AMR)

AF:

0.0535

AC:

2392

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0457

AC:

1195

AN:

26136

East Asian (EAS)

AF:

0.0680

AC:

2699

AN:

39700

South Asian (SAS)

AF:

0.0675

AC:

5818

AN:

86254

European-Finnish (FIN)

AF:

0.105

AC:

5610

AN:

53414

Middle Eastern (MID)

AF:

0.0184

AC:

106

AN:

5766

European-Non Finnish (NFE)

AF:

0.0548

AC:

60980

AN:

1111916

Other (OTH)

AF:

0.0577

AC:

3486

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

4740

9479

14219

18958

23698

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2388

4776

7164

9552

11940

<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:

0.0720

AC:

10958

AN:

152116

Hom.:

478

Cov.:

AF XY:

0.0733

AC XY:

5451

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.103

AC:

4285

AN:

41486

American (AMR)

AF:

0.0530

AC:

809

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0495

AC:

172

AN:

3472

East Asian (EAS)

AF:

0.0702

AC:

363

AN:

5174

South Asian (SAS)

AF:

0.0624

AC:

301

AN:

4824

European-Finnish (FIN)

AF:

0.106

AC:

1120

AN:

10580

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0541

AC:

3678

AN:

67994

Other (OTH)

AF:

0.0618

AC:

130

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

498

995

1493

1990

2488

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

256

384

512

640

<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:

0.0648

Hom.:

273

Bravo

AF:

0.0710

Asia WGS

AF:

0.116

AC:

402

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

Nov 20, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Li-Fraumeni syndrome 1

Benign:2

Jul 07, 2023

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:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary cancer-predisposing syndrome

Benign:1

Jun 18, 2022

Genome-Nilou Lab

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: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

-0.88

CADD

Benign

2.0

(source)

DANN

Benign

0.76

PhyloP100

0.21

PromoterAI

0.064

Neutral

(source)

RBP_binding_hub_radar

0.85

RBP_regulation_power_radar

2.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over