rs8073498

Positions:

• chr17-7666380-A-C

Variant summary

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

The ENST00000359597.8(TP53):​c.994-136T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 378,424 control chromosomes in the GnomAD database, including 25,260 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 (10683 hom., cov: 31)
  • Exomes 𝑓: 0.34 (14577 hom.)
• Consequence: TP53 ENST00000359597.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.388

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=-0.98).
• 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.994-136T>G		intron_variant		1		ENSP00000352610
TP53	ENST00000413465.6	c.783-4366T>G		intron_variant		1		ENSP00000410739
TP53	ENST00000635293.1	c.*274+522T>G		intron_variant, NMD_transcript_variant		5		ENSP00000488924

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55468 AN: 151828 Hom.: 10673 Cov.: 31

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.0584

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.329

GnomAD4 exome AF: 0.336 AC: 76196 AN: 226478 Hom.: 14577 AF XY: 0.333 AC XY: 40110 AN XY: 120476

Gnomad4 AFR exome AF: 0.407

Gnomad4 AMR exome AF: 0.220

Gnomad4 ASJ exome AF: 0.304

Gnomad4 EAS exome AF: 0.0349

Gnomad4 SAS exome AF: 0.198

Gnomad4 FIN exome AF: 0.428

Gnomad4 NFE exome AF: 0.385

Gnomad4 OTH exome AF: 0.337

GnomAD4 genome AF: 0.365 AC: 55517 AN: 151946 Hom.: 10683 Cov.: 31 AF XY: 0.358 AC XY: 26609 AN XY: 74260

Gnomad4 AFR AF: 0.408

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.0589

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.422

Gnomad4 NFE AF: 0.390

Gnomad4 OTH AF: 0.333

Alfa AF: 0.368 Hom.: 21025

Bravo AF: 0.354

Asia WGS AF: 0.195 AC: 682 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.8
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8073498; hg19: chr17-7569698; COSMIC: COSV99363901; COSMIC: COSV99363901;