chr17-7667505-G-C

Position:

• chr17-7667505-G-C

Variant summary

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

The ENST00000359597.8(TP53):​c.994-1261C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,228 control chromosomes in the GnomAD database, including 1,965 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 0.12 (1965 hom., cov: 30)
  • Exomes 𝑓: 0.047 (0 hom.)
• Consequence: TP53 ENST00000359597.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.203

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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.264 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.994-1261C>G		intron_variant		1		ENSP00000352610
TP53	ENST00000413465.6	c.783-5491C>G		intron_variant		1		ENSP00000410739
TP53	ENST00000635293.1	c.984-80C>G		intron_variant, NMD_transcript_variant		5		ENSP00000488924

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18053 AN: 152024 Hom.: 1959 Cov.: 30

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0685

Gnomad ASJ AF: 0.0351

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.0155

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0445

Gnomad OTH AF: 0.107

GnomAD4 exome AF: 0.0465 AC: 4 AN: 86 Hom.: 0 AF XY: 0.0645 AC XY: 4 AN XY: 62

Gnomad4 EAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0417

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.119 AC: 18094 AN: 152142 Hom.: 1965 Cov.: 30 AF XY: 0.118 AC XY: 8780 AN XY: 74390

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.0684

Gnomad4 ASJ AF: 0.0351

Gnomad4 EAS AF: 0.276

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.0155

Gnomad4 NFE AF: 0.0445

Gnomad4 OTH AF: 0.109

Alfa AF: 0.0262 Hom.: 28

Bravo AF: 0.130

Asia WGS AF: 0.233 AC: 809 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.6
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: rs9914052; hg19: chr17-7570823;