Variant rs35850753 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000504937.5(TP53):c.-138G>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 0.0171 in 1,531,386 control chromosomes in the GnomAD database, including 264 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 25 hom., cov: 31)

Exomes 𝑓: 0.018 ( 239 hom. )

Consequence

TP53
ENST00000504937.5 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.39

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=-0.92).

BP6

Variant 17-7675353-C-T is Benign according to our data. Variant chr17-7675353-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 670316.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0129 (1951/151066) while in subpopulation NFE AF= 0.0206 (1397/67894). AF 95% confidence interval is 0.0197. There are 25 homozygotes in gnomad4. There are 942 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1951 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TP53	NM_000546.6 linkuse as main transcript	c.376-117G>A		intron_variant		ENST00000269305.9	NP_000537.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TP53	ENST00000269305.9 linkuse as main transcript	c.376-117G>A		intron_variant		1	NM_000546.6	ENSP00000269305	P1	P04637-1

Frequencies

GnomAD3 genomes

AF:

0.0129

AC:

1950

AN:

151004

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00366

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00529

Gnomad ASJ

AF:

0.00433

Gnomad EAS

AF:

0.000391

Gnomad SAS

AF:

0.00334

Gnomad FIN

AF:

0.0267

Gnomad MID

AF:

0.00325

Gnomad NFE

AF:

0.0206

Gnomad OTH

AF:

0.00674

GnomAD4 exome

AF:

0.0176

AC:

24244

AN:

1380320

Hom.:

239

Cov.:

AF XY:

0.0174

AC XY:

11853

AN XY:

681334

show subpopulations

Gnomad4 AFR exome

AF:

0.00262

Gnomad4 AMR exome

AF:

0.00515

Gnomad4 ASJ exome

AF:

0.00591

Gnomad4 EAS exome

AF:

0.00131

Gnomad4 SAS exome

AF:

0.00405

Gnomad4 FIN exome

AF:

0.0249

Gnomad4 NFE exome

AF:

0.0203

Gnomad4 OTH exome

AF:

0.0118

GnomAD4 genome

AF:

0.0129

AC:

1951

AN:

151066

Hom.:

Cov.:

AF XY:

0.0128

AC XY:

942

AN XY:

73698

show subpopulations

Gnomad4 AFR

AF:

0.00367

Gnomad4 AMR

AF:

0.00528

Gnomad4 ASJ

AF:

0.00433

Gnomad4 EAS

AF:

0.000392

Gnomad4 SAS

AF:

0.00335

Gnomad4 FIN

AF:

0.0267

Gnomad4 NFE

AF:

0.0206

Gnomad4 OTH

AF:

0.00670

Alfa

AF:

0.0211

Hom.:

Bravo

AF:

0.0108

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 15, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.25

DANN

Benign

0.57

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