rs17887200

Variant names:

• chr17-7667753-T-C
• rs17887200
• ENST00000359597.8:c.994-1509A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

TP53 Gene-Disease associations (from GenCC):

• breast cancer

  Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
• Li-Fraumeni syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet
• Li-Fraumeni syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Genomics England PanelApp
• adrenocortical carcinoma, hereditary

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
• sarcoma

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• bone marrow failure syndrome 5

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• colorectal cancer

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• choroid plexus carcinoma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TP53	ENST00000359597.8	c.994-1509A>G		intron_variant	Intron 8 of 8	1		ENSP00000352610.4
TP53	ENST00000413465.6	c.783-5739A>G		intron_variant	Intron 6 of 6	1		ENSP00000410739.2
TP53	ENST00000714356.1	c.984-1509A>G		intron_variant	Intron 9 of 9			ENSP00000519623.1
TP53	ENST00000635293.1	n.984-328A>G		intron_variant	Intron 10 of 11	5		ENSP00000488924.1

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

African (AFR) AF: 0.0917 AC: 3809 AN: 41520

American (AMR) AF: 0.0518 AC: 791 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0159 AC: 55 AN: 3468

East Asian (EAS) AF: 0.356 AC: 1830 AN: 5136

South Asian (SAS) AF: 0.160 AC: 772 AN: 4826

European-Finnish (FIN) AF: 0.0174 AC: 184 AN: 10604

Middle Eastern (MID) AF: 0.0240 AC: 7 AN: 292

European-Non Finnish (NFE) AF: 0.0451 AC: 3067 AN: 67996

Other (OTH) AF: 0.0686 AC: 145 AN: 2114

Alfa AF: 0.0524 Hom.: 74

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
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

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