rs17887200

Positions:

• chr17-7667753-T-C

Variant summary

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

The ENST00000359597.8(TP53):​c.994-1509A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0702 in 152,152 control chromosomes in the GnomAD database, including 732 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 0.070 (732 hom., cov: 32)
• Consequence: TP53 ENST00000359597.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.43

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TP53	ENST00000359597.8	c.994-1509A>G		intron_variant		1
TP53	ENST00000413465.6	c.783-5739A>G		intron_variant		1
TP53	ENST00000635293.1	c.984-328A>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0701 AC: 10651 AN: 152034 Hom.: 730 Cov.: 32

Gnomad AFR AF: 0.0909

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0518

Gnomad ASJ AF: 0.0159

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.0174

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.0451

Gnomad OTH AF: 0.0664

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

GnomAD4 genome AF: 0.0702 AC: 10681 AN: 152152 Hom.: 732 Cov.: 32 AF XY: 0.0712 AC XY: 5299 AN XY: 74384

Gnomad4 AFR AF: 0.0917

Gnomad4 AMR AF: 0.0518

Gnomad4 ASJ AF: 0.0159

Gnomad4 EAS AF: 0.356

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.0174

Gnomad4 NFE AF: 0.0451

Gnomad4 OTH AF: 0.0686

Alfa AF: 0.0524 Hom.: 65

Bravo AF: 0.0748

Asia WGS AF: 0.240 AC: 832 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.045
DANN	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17887200; hg19: chr17-7571071; COSMIC: COSV53538686; COSMIC: COSV53538686;