Variant 17-7666228-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The ENST00000359597.8(TP53):c.1010G>C(p.Arg337Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00183 in 649,822 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.0060 ( 10 hom., cov: 31)

Exomes 𝑓: 0.00056 ( 1 hom. )

Consequence

TP53
ENST00000359597.8 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 0.721

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005035609).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.006 (912/152028) while in subpopulation AFR AF= 0.0211 (875/41478). AF 95% confidence interval is 0.0199. There are 10 homozygotes in gnomad4. There are 429 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High AC in GnomAd4 at 912 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein
TP53	ENST00000359597.8 linkuse as main transcript	c.1010G>C	p.Arg337Thr	missense_variant	9/9	1	ENSP00000352610
TP53	ENST00000413465.6 linkuse as main transcript	c.783-4214G>C		intron_variant		1	ENSP00000410739
TP53	ENST00000635293.1 linkuse as main transcript	c.*274+674G>C		intron_variant, NMD_transcript_variant		5	ENSP00000488924

Frequencies

GnomAD3 genomes

AF:

0.00600

AC:

912

AN:

151910

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0212

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00184

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.000545

AC:

AN:

99062

Hom.:

AF XY:

0.000471

AC XY:

AN XY:

55176

show subpopulations

Gnomad AFR exome

AF:

0.0111

Gnomad AMR exome

AF:

0.000414

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000600

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000250

Gnomad OTH exome

AF:

0.000667

GnomAD4 exome

AF:

0.000556

AC:

277

AN:

497794

Hom.:

Cov.:

AF XY:

0.000462

AC XY:

125

AN XY:

270802

show subpopulations

Gnomad4 AFR exome

AF:

0.0180

Gnomad4 AMR exome

AF:

0.000329

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000372

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000137

Gnomad4 OTH exome

AF:

0.000883

GnomAD4 genome

AF:

0.00600

AC:

912

AN:

152028

Hom.:

Cov.:

AF XY:

0.00577

AC XY:

429

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.0211

Gnomad4 AMR

AF:

0.00184

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000736

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00367

Hom.:

Bravo

AF:

0.00687

ExAC

AF:

0.000591

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not specified

Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.22

CADD

Benign

2.3

DANN

Benign

0.55

DEOGEN2

Benign

0.017

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.29

MetaRNN

Benign

0.0050

MetaSVM

Uncertain

0.54

MutationTaster

Benign

1.0

N;N

PROVEAN

Benign

-1.4

REVEL

Benign

0.22

Sift

Uncertain

0.019

Sift4G

Uncertain

0.015

Vest4

0.19

MVP

0.71

ClinPred

0.0082

GERP RS

0.43

Splicing

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