rs8064946

chr17-7685993-G-Cchr17-7685993-G-T

Variant summary

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

The NM_000546.6(TP53):c.-29+1384C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 152,228 control chromosomes in the GnomAD database, including 13,621 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 0.32 (13621 hom., cov: 33)
  • Exomes 𝑓: 0.063 (0 hom.)
• Consequence: TP53 NM_000546.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.830

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TP53	NM_000546.6	c.-29+1384C>G		intron_variant		ENST00000269305.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TP53	ENST00000269305.9	c.-29+1384C>G		intron_variant		1	NM_000546.6	P1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47862 AN: 152094 Hom.: 13578 Cov.: 33

Gnomad AFR AF: 0.759

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.0618

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.267

GnomAD4 exome AF: 0.0625 AC: 1 AN: 16 Hom.: 0 Cov.: 0 AF XY: 0.0714 AC XY: 1 AN XY: 14

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.315 AC: 47968 AN: 152212 Hom.: 13621 Cov.: 33 AF XY: 0.309 AC XY: 23033 AN XY: 74430

Gnomad4 AFR AF: 0.759

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.326

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.0618

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.268

Alfa AF: 0.0952 Hom.: 230

Bravo AF: 0.345

Asia WGS AF: 0.318 AC: 1104 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	3.1
Dann	Benign	0.53

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: rs8064946; hg19: chr17-7589311;