rs12951053

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.782+92T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,004,186 control chromosomes in the GnomAD database, including 7,111 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 1031 hom., cov: 30)

Exomes 𝑓: 0.10 ( 6080 hom. )

Consequence

TP53
NM_000546.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.64

Publications

97 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=-0.9).

BP6

Variant 17-7674089-A-C is Benign according to our data. Variant chr17-7674089-A-C is described in ClinVar as Benign. ClinVar VariationId is 1243959.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TP53	NM_000546.6 link	c.782+92T>G		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
TP53	ENST00000269305.9 link	c.782+92T>G		intron_variant	Intron 7 of 10	1	NM_000546.6	ENSP00000269305.4		P04637-1

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15795

AN:

151722

Hom.:

1034

Cov.:

show subpopulations

Gnomad AFR

AF:

0.118

Gnomad AMI

AF:

0.0560

Gnomad AMR

AF:

0.119

Gnomad ASJ

AF:

0.0710

Gnomad EAS

AF:

0.321

Gnomad SAS

AF:

0.199

Gnomad FIN

AF:

0.0516

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0802

Gnomad OTH

AF:

0.0908

GnomAD4 exome

AF:

0.101

AC:

86008

AN:

852346

Hom.:

6080

AF XY:

0.105

AC XY:

46657

AN XY:

445052

show subpopulations

African (AFR)

AF:

0.122

AC:

2654

AN:

21752

American (AMR)

AF:

0.145

AC:

5633

AN:

38912

Ashkenazi Jewish (ASJ)

AF:

0.0692

AC:

1508

AN:

21784

East Asian (EAS)

AF:

0.301

AC:

10926

AN:

36264

South Asian (SAS)

AF:

0.198

AC:

14258

AN:

71982

European-Finnish (FIN)

AF:

0.0543

AC:

2785

AN:

51268

Middle Eastern (MID)

AF:

0.0701

AC:

249

AN:

3550

European-Non Finnish (NFE)

AF:

0.0776

AC:

43981

AN:

566626

Other (OTH)

AF:

0.0998

AC:

4014

AN:

40208

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

4422

8844

13265

17687

22109

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1230

2460

3690

4920

6150

<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:

0.104

AC:

15811

AN:

151840

Hom.:

1031

Cov.:

AF XY:

0.106

AC XY:

7848

AN XY:

74200

show subpopulations

African (AFR)

AF:

0.119

AC:

4915

AN:

41414

American (AMR)

AF:

0.119

AC:

1808

AN:

15222

Ashkenazi Jewish (ASJ)

AF:

0.0710

AC:

246

AN:

3466

East Asian (EAS)

AF:

0.321

AC:

1639

AN:

5104

South Asian (SAS)

AF:

0.197

AC:

948

AN:

4808

European-Finnish (FIN)

AF:

0.0516

AC:

545

AN:

10558

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0802

AC:

5450

AN:

67960

Other (OTH)

AF:

0.0936

AC:

197

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

690

1381

2071

2762

3452

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

190

380

570

760

950

<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:

0.0929

Hom.:

816

Bravo

AF:

0.108

Asia WGS

AF:

0.238

AC:

826

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Li-Fraumeni syndrome 1

Benign:1

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

-0.90

CADD

Benign

0.49

(source)

DANN

Benign

0.71

PhyloP100

-1.6

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