rs1614984

Variant names:

• chr17-7668134-G-A
• rs1614984
• ENST00000359597.8:c.994-1890C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-7668134-G-A
• chr17-7668134-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000359597.8(TP53):​c.994-1890C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 152,016 control chromosomes in the GnomAD database, including 12,254 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.40 (12254 hom., cov: 32)
• Consequence: TP53 ENST00000359597.8 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.750
• Publications: 18 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 17-7668134-G-A is Benign according to our data. Variant chr17-7668134-G-A is described in ClinVar as Benign. ClinVar VariationId is 1294447.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.428 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.994-1890C>T		intron_variant	Intron 8 of 8	1		ENSP00000352610.4
TP53	ENST00000413465.6	c.782+6047C>T		intron_variant	Intron 6 of 6	1		ENSP00000410739.2
TP53	ENST00000714356.1	c.984-1890C>T		intron_variant	Intron 9 of 9			ENSP00000519623.1
TP53	ENST00000635293.1	n.984-709C>T		intron_variant	Intron 10 of 11	5		ENSP00000488924.1

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60588 AN: 151894 Hom.: 12244 Cov.: 32

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.308

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.372

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

GnomAD4 genome AF: 0.399 AC: 60625 AN: 152016 Hom.: 12254 Cov.: 32 AF XY: 0.394 AC XY: 29308 AN XY: 74294

African (AFR) AF: 0.388 AC: 16079 AN: 41450

American (AMR) AF: 0.304 AC: 4640 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 1167 AN: 3472

East Asian (EAS) AF: 0.336 AC: 1734 AN: 5166

South Asian (SAS) AF: 0.364 AC: 1757 AN: 4826

European-Finnish (FIN) AF: 0.435 AC: 4596 AN: 10564

Middle Eastern (MID) AF: 0.301 AC: 88 AN: 292

European-Non Finnish (NFE) AF: 0.432 AC: 29336 AN: 67954

Other (OTH) AF: 0.379 AC: 801 AN: 2114

Alfa AF: 0.407 Hom.: 9848

Bravo AF: 0.386

Asia WGS AF: 0.397 AC: 1379 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 14, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.6
DANN	Benign	0.68
PhyloP100		0.75
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: rs1614984; hg19: chr17-7571452;