rs17882227

Positions:

• chr17-7685242-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000546.6(TP53):​c.-29+2135T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,122 control chromosomes in the GnomAD database, including 2,310 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (2310 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: TP53 NM_000546.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TP53	NM_000546.6	c.-29+2135T>C		intron_variant		ENST00000269305.9	NP_000537.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TP53	ENST00000269305.9	c.-29+2135T>C		intron_variant		1	NM_000546.6	ENSP00000269305	P1

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22434 AN: 152004 Hom.: 2306 Cov.: 32

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.0806

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.0472

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0760

Gnomad OTH AF: 0.125

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.148 AC: 22468 AN: 152122 Hom.: 2310 Cov.: 32 AF XY: 0.148 AC XY: 10992 AN XY: 74410

Gnomad4 AFR AF: 0.275

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.0806

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.0472

Gnomad4 NFE AF: 0.0760

Gnomad4 OTH AF: 0.127

Alfa AF: 0.116 Hom.: 250

Bravo AF: 0.157

Asia WGS AF: 0.253 AC: 876 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	8.7
DANN	Benign	0.86

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: rs17882227; hg19: chr17-7588560;