Variant chr17-7675327-C-T 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 ENST00000504937.5(TP53):c.-112G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.864 in 1,549,438 control chromosomes in the GnomAD database, including 580,408 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.84 ( 53539 hom., cov: 29)

Exomes 𝑓: 0.87 ( 526869 hom. )

Consequence

TP53
ENST00000504937.5 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.320

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:

TP53 (HGNC:):

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=-0.87).

BP6

Variant 17-7675327-C-T is Benign according to our data. Variant chr17-7675327-C-T is described in ClinVar as [Benign]. Clinvar id is 440348.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TP53	NM_000546.6 linkuse as main transcript	c.376-91G>A		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 linkuse as main transcript	c.376-91G>A		intron_variant		1	NM_000546.6	ENSP00000269305.4		P04637-1

Frequencies

GnomAD3 genomes

AF:

0.837

AC:

126886

AN:

151524

Hom.:

53502

Cov.:

show subpopulations

Gnomad AFR

AF:

0.737

Gnomad AMI

AF:

0.832

Gnomad AMR

AF:

0.887

Gnomad ASJ

AF:

0.841

Gnomad EAS

AF:

0.967

Gnomad SAS

AF:

0.800

Gnomad FIN

AF:

0.889

Gnomad MID

AF:

0.699

Gnomad NFE

AF:

0.873

Gnomad OTH

AF:

0.837

GnomAD4 exome

AF:

0.867

AC:

1212266

AN:

1397800

Hom.:

526869

Cov.:

AF XY:

0.865

AC XY:

597421

AN XY:

691020

show subpopulations

Gnomad4 AFR exome

AF:

0.727

Gnomad4 AMR exome

AF:

0.919

Gnomad4 ASJ exome

AF:

0.834

Gnomad4 EAS exome

AF:

0.972

Gnomad4 SAS exome

AF:

0.793

Gnomad4 FIN exome

AF:

0.890

Gnomad4 NFE exome

AF:

0.873

Gnomad4 OTH exome

AF:

0.861

GnomAD4 genome

AF:

0.837

AC:

126969

AN:

151638

Hom.:

53539

Cov.:

AF XY:

0.837

AC XY:

62038

AN XY:

74088

show subpopulations

Gnomad4 AFR

AF:

0.737

Gnomad4 AMR

AF:

0.887

Gnomad4 ASJ

AF:

0.841

Gnomad4 EAS

AF:

0.967

Gnomad4 SAS

AF:

0.800

Gnomad4 FIN

AF:

0.889

Gnomad4 NFE

AF:

0.873

Gnomad4 OTH

AF:

0.839

Alfa

AF:

0.856

Hom.:

39180

Bravo

AF:

0.835

Asia WGS

AF:

0.887

AC:

3084

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	Nov 03, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Jul 02, 2018

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

3.0

DANN

Benign

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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