rs17884306

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.*826G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0505 in 223,876 control chromosomes in the GnomAD database, including 368 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.052 ( 268 hom., cov: 30)

Exomes 𝑓: 0.048 ( 100 hom. )

Consequence

TP53
NM_000546.6 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.390

Publications

27 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: ClinGen, G2P, Labcorp Genetics (formerly Invitae), 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 17-7668783-C-T is Benign according to our data. Variant chr17-7668783-C-T is described in ClinVar as Benign. ClinVar VariationId is 325623.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0688 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000546.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TP53	NM_000546.6	MANE Select	c.*826G>A	3_prime_UTR	Exon 11 of 11	NP_000537.3
TP53	NM_001126112.3		c.*826G>A	3_prime_UTR	Exon 11 of 11	NP_001119584.1	K7PPA8
TP53	NM_001407262.1		c.*826G>A	3_prime_UTR	Exon 12 of 12	NP_001394191.1	K7PPA8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TP53	ENST00000269305.9	TSL:1 MANE Select	c.*826G>A	3_prime_UTR	Exon 11 of 11	ENSP00000269305.4	P04637-1
TP53	ENST00000445888.6	TSL:1	c.*826G>A	3_prime_UTR	Exon 11 of 11	ENSP00000391478.2	P04637-1
TP53	ENST00000610292.4	TSL:1	c.*826G>A	3_prime_UTR	Exon 10 of 10	ENSP00000478219.1	P04637-4

Frequencies

GnomAD3 genomes

AF:

0.0516

AC:

7572

AN:

146758

Hom.:

264

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0286

Gnomad AMI

AF:

0.107

Gnomad AMR

AF:

0.0454

Gnomad ASJ

AF:

0.0500

Gnomad EAS

AF:

0.0713

Gnomad SAS

AF:

0.0749

Gnomad FIN

AF:

0.117

Gnomad MID

AF:

0.00667

Gnomad NFE

AF:

0.0541

Gnomad OTH

AF:

0.0420

GnomAD4 exome

AF:

0.0479

AC:

3692

AN:

77010

Hom.:

100

Cov.:

AF XY:

0.0484

AC XY:

1724

AN XY:

35588

show subpopulations

African (AFR)

AF:

0.0274

AC:

AN:

3580

American (AMR)

AF:

0.0374

AC:

AN:

2354

Ashkenazi Jewish (ASJ)

AF:

0.0478

AC:

232

AN:

4858

East Asian (EAS)

AF:

0.0599

AC:

656

AN:

10948

South Asian (SAS)

AF:

0.0912

AC:

AN:

658

European-Finnish (FIN)

AF:

0.0357

AC:

AN:

224

Middle Eastern (MID)

AF:

0.0148

AC:

AN:

472

European-Non Finnish (NFE)

AF:

0.0471

AC:

2241

AN:

47572

Other (OTH)

AF:

0.0476

AC:

302

AN:

6344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

162

325

487

650

812

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.0518

AC:

7603

AN:

146866

Hom.:

268

Cov.:

AF XY:

0.0546

AC XY:

3883

AN XY:

71146

show subpopulations

African (AFR)

AF:

0.0287

AC:

1132

AN:

39410

American (AMR)

AF:

0.0455

AC:

655

AN:

14390

Ashkenazi Jewish (ASJ)

AF:

0.0500

AC:

173

AN:

3460

East Asian (EAS)

AF:

0.0719

AC:

361

AN:

5022

South Asian (SAS)

AF:

0.0753

AC:

353

AN:

4690

European-Finnish (FIN)

AF:

0.117

AC:

1085

AN:

9298

Middle Eastern (MID)

AF:

0.00714

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.0541

AC:

3647

AN:

67420

Other (OTH)

AF:

0.0495

AC:

AN:

1998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

340

680

1021

1361

1701

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

288

384

480

<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:

0.0555

Hom.:

Bravo

AF:

0.0456

Asia WGS

AF:

0.126

AC:

436

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Li-Fraumeni syndrome 1 (2)

not provided (2)

Hereditary cancer-predisposing syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.2

(source)

DANN

Benign

0.74

PhyloP100

-0.39

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over