rs17886760

Positions:

• chr17-7667660-T-C

Variant summary

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

The ENST00000359597.8(TP53):​c.994-1416A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0798 in 152,058 control chromosomes in the GnomAD database, including 811 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 0.080 (811 hom., cov: 32)
• Consequence: TP53 ENST00000359597.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.7667660T>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TP53	ENST00000359597.8	c.994-1416A>G		intron_variant		1		ENSP00000352610.4
TP53	ENST00000413465.6	c.783-5646A>G		intron_variant		1		ENSP00000410739.2
TP53	ENST00000635293.1	n.984-235A>G		intron_variant		5		ENSP00000488924.1

Frequencies

GnomAD3 genomes AF: 0.0797 AC: 12106 AN: 151940 Hom.: 810 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0483

Gnomad ASJ AF: 0.0289

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.0151

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0435

Gnomad OTH AF: 0.0758

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

GnomAD4 genome AF: 0.0798 AC: 12130 AN: 152058 Hom.: 811 Cov.: 32 AF XY: 0.0804 AC XY: 5978 AN XY: 74332

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.0483

Gnomad4 ASJ AF: 0.0289

Gnomad4 EAS AF: 0.268

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.0151

Gnomad4 NFE AF: 0.0435

Gnomad4 OTH AF: 0.0779

Alfa AF: 0.0522 Hom.: 66

Bravo AF: 0.0841

Asia WGS AF: 0.220 AC: 764 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.5
DANN	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17886760; hg19: chr17-7570978;