rs17880560

chr17-7668169-A-AGCCGTG

Variant summary

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

The ENST00000359597.8(TP53):c.994-1926_994-1925insCACGGC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 151,810 control chromosomes in the GnomAD database, including 6,581 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.29 (6581 hom., cov: 15)
• Consequence: TP53 ENST00000359597.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.39

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 17-7668169-A-AGCCGTG is Benign according to our data. Variant chr17-7668169-A-AGCCGTG is described in ClinVar as [Benign]. Clinvar id is 1170064.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TP53	ENST00000359597.8	c.994-1926_994-1925insCACGGC		intron_variant		1
TP53	ENST00000413465.6	c.782+6011_782+6012insCACGGC		intron_variant		1
TP53	ENST00000635293.1	c.984-745_984-744insCACGGC		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43449 AN: 151690 Hom.: 6578 Cov.: 15

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.0586

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.268

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.286 AC: 43466 AN: 151810 Hom.: 6581 Cov.: 15 AF XY: 0.283 AC XY: 21011 AN XY: 74172

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.0592

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.385

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.273

Alfa AF: 0.314 Hom.: 792

Asia WGS AF: 0.180 AC: 626 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Li-Fraumeni syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

- -

Li-Fraumeni syndrome 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jun 18, 2022

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2019

This variant is associated with the following publications: (PMID: 24336192) -

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17880560; hg19: chr17-7571487;