Variant rs12947788 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000546.6(TP53):c.782+72C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0995 in 1,155,766 control chromosomes in the GnomAD database, including 7,796 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 1035 hom., cov: 31)

Exomes 𝑓: 0.099 ( 6761 hom. )

Consequence

TP53
NM_000546.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.189

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 17-7674109-G-A is Benign according to our data. Variant chr17-7674109-G-A is described in ClinVar as [Benign]. Clinvar id is 1243351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674109-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TP53	NM_000546.6 link	c.782+72C>T		intron_variant		ENST00000269305.9	NP_000537.3	P04637-1K7PPA8Q53GA5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TP53	ENST00000269305.9 link	c.782+72C>T		intron_variant		1	NM_000546.6	ENSP00000269305.4		P04637-1

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15808

AN:

151834

Hom.:

1038

Cov.:

show subpopulations

Gnomad AFR

AF:

0.118

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.119

Gnomad ASJ

AF:

0.0709

Gnomad EAS

AF:

0.321

Gnomad SAS

AF:

0.199

Gnomad FIN

AF:

0.0516

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0803

Gnomad OTH

AF:

0.0909

GnomAD4 exome

AF:

0.0988

AC:

99213

AN:

1003814

Hom.:

6761

AF XY:

0.102

AC XY:

53065

AN XY:

518090

show subpopulations

Gnomad4 AFR exome

AF:

0.121

Gnomad4 AMR exome

AF:

0.147

Gnomad4 ASJ exome

AF:

0.0693

Gnomad4 EAS exome

AF:

0.301

Gnomad4 SAS exome

AF:

0.199

Gnomad4 FIN exome

AF:

0.0542

Gnomad4 NFE exome

AF:

0.0778

Gnomad4 OTH exome

AF:

0.0993

GnomAD4 genome

AF:

0.104

AC:

15824

AN:

151952

Hom.:

1035

Cov.:

AF XY:

0.106

AC XY:

7852

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.119

Gnomad4 AMR

AF:

0.119

Gnomad4 ASJ

AF:

0.0709

Gnomad4 EAS

AF:

0.322

Gnomad4 SAS

AF:

0.197

Gnomad4 FIN

AF:

0.0516

Gnomad4 NFE

AF:

0.0803

Gnomad4 OTH

AF:

0.0938

Alfa

AF:

0.0939

Hom.:

Bravo

AF:

0.108

Asia WGS

AF:

0.238

AC:

824

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Li-Fraumeni syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jun 18, 2022

- -

Hereditary cancer-predisposing syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jun 18, 2022

- -

Hereditary breast ovarian cancer syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

National Health Laboratory Service, Universitas Academic Hospital and University of the Free State

Apr 19, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

6.2

DANN

Benign

0.69

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over