17-7676325-CCCCCAGCCCTCCAGGTCCCCAGCCCTCCAGGT-CCCCCAGCCCTCCAGGT

Position:

• chr17-7676325-CCCCCAGCCCTCCAGGTCCCCAGCCCTCCAGGT-CCCCCAGCCCTCCAGGT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000546.6(TP53):​c.96+41_97-54delACCTGGAGGGCTGGGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.849 in 1,597,830 control chromosomes in the GnomAD database, including 578,214 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.83 (51944 hom., cov: 0)
  • Exomes 𝑓: 0.85 (526270 hom.)
• Consequence: TP53 NM_000546.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 1.06

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 17-7676325-CCCCCAGCCCTCCAGGT-C is Benign according to our data. Variant chr17-7676325-CCCCCAGCCCTCCAGGT-C is described in ClinVar as [Benign]. Clinvar id is 440349.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676325-CCCCCAGCCCTCCAGGT-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TP53	NM_000546.6	c.96+41_97-54delACCTGGAGGGCTGGGG		intron_variant		ENST00000269305.9	NP_000537.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TP53	ENST00000269305.9	c.96+41_97-54delACCTGGAGGGCTGGGG		intron_variant		1	NM_000546.6	ENSP00000269305.4

Frequencies

GnomAD3 genomes AF: 0.827 AC: 124754 AN: 150858 Hom.: 51911 Cov.: 0

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.829

Gnomad AMR AF: 0.876

Gnomad ASJ AF: 0.825

Gnomad EAS AF: 0.963

Gnomad SAS AF: 0.791

Gnomad FIN AF: 0.887

Gnomad MID AF: 0.692

Gnomad NFE AF: 0.856

Gnomad OTH AF: 0.823

GnomAD4 exome AF: 0.851 AC: 1231108 AN: 1446856 Hom.: 526270 AF XY: 0.848 AC XY: 610979 AN XY: 720398

Gnomad4 AFR exome AF: 0.722

Gnomad4 AMR exome AF: 0.911

Gnomad4 ASJ exome AF: 0.819

Gnomad4 EAS exome AF: 0.970

Gnomad4 SAS exome AF: 0.782

Gnomad4 FIN exome AF: 0.884

Gnomad4 NFE exome AF: 0.854

Gnomad4 OTH exome AF: 0.846

GnomAD4 genome AF: 0.827 AC: 124834 AN: 150974 Hom.: 51944 Cov.: 0 AF XY: 0.827 AC XY: 60984 AN XY: 73706

Gnomad4 AFR AF: 0.733

Gnomad4 AMR AF: 0.876

Gnomad4 ASJ AF: 0.825

Gnomad4 EAS AF: 0.963

Gnomad4 SAS AF: 0.790

Gnomad4 FIN AF: 0.887

Gnomad4 NFE AF: 0.856

Gnomad4 OTH AF: 0.825

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Hereditary cancer-predisposing syndrome Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jun 18, 2022	- -
Benign, flagged submission	clinical testing	GeneDx	Oct 15, 2013	The variant is found in HEREDICANCER,COLO-HEREDIC,BR-OV-HEREDIC panel(s). -

Li-Fraumeni syndrome 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jun 18, 2022

- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Jul 02, 2018

- -

Breast and/or ovarian cancer Benign:1

Benign, criteria provided, single submitter

clinical testing

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Apr 21, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs59758982; hg19: chr17-7579643;