17-7676325-CCCCCAGCCCTCCAGGTCCCCAGCCCTCCAGGT-CCCCCAGCCCTCCAGGT

Variant names:

• chr17-7676325-CCCCCAGCCCTCCAGGT-C
• rs59758982
• NM_000546.6:c.96+41_97-54delACCTGGAGGGCTGGGG

Variant summary

Our verdict is Benign. The variant received -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. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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:7
• Conservation: PhyloP100: 1.06
• Publications: 12 publications found

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 Gene-Disease associations (from GenCC):

• breast cancer

  Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
• Li-Fraumeni syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Orphanet
• Li-Fraumeni syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Genomics England PanelApp
• adrenocortical carcinoma, hereditary

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
• sarcoma

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• bone marrow failure syndrome 5

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• colorectal cancer

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• choroid plexus carcinoma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 440349.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000546.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TP53	NM_000546.6	MANE Select	c.96+41_97-54delACCTGGAGGGCTGGGG		intron	N/A	NP_000537.3
	TP53	NM_001126112.3		c.96+41_97-54delACCTGGAGGGCTGGGG		intron	N/A	NP_001119584.1	K7PPA8
	TP53	NM_001407262.1		c.96+41_97-54delACCTGGAGGGCTGGGG		intron	N/A	NP_001394191.1	K7PPA8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TP53	ENST00000269305.9	TSL:1 MANE Select	c.96+41_97-54delACCTGGAGGGCTGGGG		intron	N/A	ENSP00000269305.4	P04637-1
	TP53	ENST00000445888.6	TSL:1	c.96+41_97-54delACCTGGAGGGCTGGGG		intron	N/A	ENSP00000391478.2	P04637-1
	TP53	ENST00000610292.4	TSL:1	c.-22+41_-21-54delACCTGGAGGGCTGGGG		intron	N/A	ENSP00000478219.1	P04637-4

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

African (AFR) AF: 0.722 AC: 23969 AN: 33206

American (AMR) AF: 0.911 AC: 40708 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.819 AC: 21332 AN: 26060

East Asian (EAS) AF: 0.970 AC: 38414 AN: 39606

South Asian (SAS) AF: 0.782 AC: 66915 AN: 85592

European-Finnish (FIN) AF: 0.884 AC: 47033 AN: 53228

Middle Eastern (MID) AF: 0.686 AC: 3926 AN: 5722

European-Non Finnish (NFE) AF: 0.854 AC: 938196 AN: 1098952

Other (OTH) AF: 0.846 AC: 50615 AN: 59818

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

African (AFR) AF: 0.733 AC: 30069 AN: 41020

American (AMR) AF: 0.876 AC: 13228 AN: 15106

Ashkenazi Jewish (ASJ) AF: 0.825 AC: 2862 AN: 3470

East Asian (EAS) AF: 0.963 AC: 4921 AN: 5108

South Asian (SAS) AF: 0.790 AC: 3757 AN: 4754

European-Finnish (FIN) AF: 0.887 AC: 9318 AN: 10500

Middle Eastern (MID) AF: 0.690 AC: 200 AN: 290

European-Non Finnish (NFE) AF: 0.856 AC: 58003 AN: 67730

Other (OTH) AF: 0.825 AC: 1728 AN: 2094

Alfa AF: 0.795 Hom.: 2019

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Hereditary cancer-predisposing syndrome (3)
-	-	1	Breast and/or ovarian cancer (1)
-	-	1	Li-Fraumeni syndrome 1 (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs59758982; hg19: chr17-7579643; COSMIC: COSV53698664;