rs9893249

Positions:

• chr17-7666871-T-C

Variant summary

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

The ENST00000359597.8(TP53):​c.994-627A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 152,184 control chromosomes in the GnomAD database, including 10,710 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 0.37 (10701 hom., cov: 32)
  • Exomes 𝑓: 0.41 (9 hom.)
• Consequence: TP53 ENST00000359597.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0700

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TP53	ENST00000359597.8	c.994-627A>G		intron_variant		1		ENSP00000352610
TP53	ENST00000413465.6	c.783-4857A>G		intron_variant		1		ENSP00000410739
TP53	ENST00000635293.1	c.*274+31A>G		intron_variant, NMD_transcript_variant		5		ENSP00000488924

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55535 AN: 151970 Hom.: 10692 Cov.: 32

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.0585

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.330

GnomAD4 exome AF: 0.408 AC: 40 AN: 98 Hom.: 9 Cov.: 0 AF XY: 0.403 AC XY: 25 AN XY: 62

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 1.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.417

Gnomad4 OTH exome AF: 0.667

GnomAD4 genome AF: 0.365 AC: 55582 AN: 152086 Hom.: 10701 Cov.: 32 AF XY: 0.359 AC XY: 26657 AN XY: 74336

Gnomad4 AFR AF: 0.408

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.0590

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.422

Gnomad4 NFE AF: 0.390

Gnomad4 OTH AF: 0.333

Alfa AF: 0.385 Hom.: 2702

Bravo AF: 0.354

Asia WGS AF: 0.195 AC: 681 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.6
DANN	Benign	0.58

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9893249; hg19: chr17-7570189;