17-7676483-G-C

Variant names:

Variant summary

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

The ENST00000610292.4(TP53):c.-123C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 1,591,856 control chromosomes in the GnomAD database, including 397,543 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 33859 hom., cov: 29)

Exomes 𝑓: 0.71 ( 363684 hom. )

Consequence

TP53
ENST00000610292.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: 0.128

Publications

90 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=-0.83).

BP6

Variant 17-7676483-G-C is Benign according to our data. Variant chr17-7676483-G-C is described in ClinVar as Benign. ClinVar VariationId is 137691.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TP53	NM_000546.6 link	c.74+38C>G		intron_variant	Intron 2 of 10	ENST00000269305.9	NP_000537.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TP53	ENST00000269305.9 link	c.74+38C>G		intron_variant	Intron 2 of 10	1	NM_000546.6	ENSP00000269305.4

Frequencies

GnomAD3 genomes

AF:

0.660

AC:

100053

AN:

151570

Hom.:

33859

Cov.:

show subpopulations

Gnomad AFR

AF:

0.515

Gnomad AMI

AF:

0.669

Gnomad AMR

AF:

0.710

Gnomad ASJ

AF:

0.715

Gnomad EAS

AF:

0.574

Gnomad SAS

AF:

0.519

Gnomad FIN

AF:

0.726

Gnomad MID

AF:

0.639

Gnomad NFE

AF:

0.740

Gnomad OTH

AF:

0.685

GnomAD2 exomes

AF:

0.673

AC:

166700

AN:

247548

AF XY:

0.667

show subpopulations

Gnomad AFR exome

AF:

0.516

Gnomad AMR exome

AF:

0.718

Gnomad ASJ exome

AF:

0.710

Gnomad EAS exome

AF:

0.571

Gnomad FIN exome

AF:

0.719

Gnomad NFE exome

AF:

0.732

Gnomad OTH exome

AF:

0.694

GnomAD4 exome

AF:

0.708

AC:

1020340

AN:

1440172

Hom.:

363684

Cov.:

AF XY:

0.703

AC XY:

503952

AN XY:

717364

show subpopulations

African (AFR)

AF:

0.503

AC:

16760

AN:

33294

American (AMR)

AF:

0.719

AC:

32091

AN:

44644

Ashkenazi Jewish (ASJ)

AF:

0.712

AC:

18519

AN:

26012

East Asian (EAS)

AF:

0.604

AC:

23952

AN:

39624

South Asian (SAS)

AF:

0.504

AC:

43370

AN:

86008

European-Finnish (FIN)

AF:

0.723

AC:

38374

AN:

53088

Middle Eastern (MID)

AF:

0.603

AC:

3455

AN:

5728

European-Non Finnish (NFE)

AF:

0.735

AC:

802203

AN:

1092010

Other (OTH)

AF:

0.696

AC:

41616

AN:

59764

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

17315

34631

51946

69262

86577

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19584

39168

58752

78336

97920

<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:

0.660

AC:

100079

AN:

151684

Hom.:

33859

Cov.:

AF XY:

0.656

AC XY:

48622

AN XY:

74104

show subpopulations

African (AFR)

AF:

0.515

AC:

21280

AN:

41348

American (AMR)

AF:

0.711

AC:

10807

AN:

15208

Ashkenazi Jewish (ASJ)

AF:

0.715

AC:

2482

AN:

3470

East Asian (EAS)

AF:

0.573

AC:

2931

AN:

5116

South Asian (SAS)

AF:

0.521

AC:

2507

AN:

4812

European-Finnish (FIN)

AF:

0.726

AC:

7622

AN:

10498

Middle Eastern (MID)

AF:

0.633

AC:

186

AN:

294

European-Non Finnish (NFE)

AF:

0.740

AC:

50235

AN:

67928

Other (OTH)

AF:

0.676

AC:

1420

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1660

3320

4979

6639

8299

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

792

1584

2376

3168

3960

<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:

0.688

Hom.:

6716

Bravo

AF:

0.656

Asia WGS

AF:

0.526

AC:

1831

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Mayo Clinic Laboratories, Mayo Clinic

Significance:Likely 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

- -

Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute

Significance:Benign

Review Status:no assertion criteria provided

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

- -

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

not provided

Benign:2

Nov 29, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

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

- -

Hereditary cancer-predisposing syndrome

Benign:2

Mar 31, 2015

Color Diagnostics, LLC DBA Color Health

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

- -

Li-Fraumeni syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.83

CADD

Benign

1.2

(source)

DANN

Benign

0.57

PhyloP100

0.13

PromoterAI

-0.070

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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