rs8079544

chr17-7676734-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000546.6(TP53):c.-28-112G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0626 in 768,624 control chromosomes in the GnomAD database, including 1,792 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.073 (499 hom., cov: 31)
  • Exomes 𝑓: 0.060 (1293 hom.)
• Consequence: TP53 NM_000546.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.69

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 17-7676734-C-T is Benign according to our data. Variant chr17-7676734-C-T is described in ClinVar as [Benign]. Clinvar id is 1292419.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TP53	NM_000546.6	c.-28-112G>A		intron_variant		ENST00000269305.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TP53	ENST00000269305.9	c.-28-112G>A		intron_variant		1	NM_000546.6	P1

Frequencies

GnomAD3 genomes AF: 0.0726 AC: 11035 AN: 152000 Hom.: 497 Cov.: 31

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.0550

Gnomad ASJ AF: 0.0510

Gnomad EAS AF: 0.0653

Gnomad SAS AF: 0.0670

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0543

Gnomad OTH AF: 0.0575

GnomAD4 exome AF: 0.0601 AC: 37066 AN: 616506 Hom.: 1293 AF XY: 0.0599 AC XY: 19688 AN XY: 328820

Gnomad4 AFR exome AF: 0.100

Gnomad4 AMR exome AF: 0.0543

Gnomad4 ASJ exome AF: 0.0487

Gnomad4 EAS exome AF: 0.0653

Gnomad4 SAS exome AF: 0.0739

Gnomad4 FIN exome AF: 0.101

Gnomad4 NFE exome AF: 0.0531

Gnomad4 OTH exome AF: 0.0582

GnomAD4 genome AF: 0.0727 AC: 11065 AN: 152118 Hom.: 499 Cov.: 31 AF XY: 0.0743 AC XY: 5523 AN XY: 74366

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.0552

Gnomad4 ASJ AF: 0.0510

Gnomad4 EAS AF: 0.0658

Gnomad4 SAS AF: 0.0670

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.0544

Gnomad4 OTH AF: 0.0621

Alfa AF: 0.0560 Hom.: 331

Bravo AF: 0.0718

Asia WGS AF: 0.121 AC: 419 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 24, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.69
Dann	Benign	0.26

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

Other links and lift over

dbSNP: rs8079544; hg19: chr17-7580052;