rs9903378

Positions:

• chr17-7684688-A-C

Variant summary

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

The NM_000546.6(TP53):​c.-29+2689T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 151,912 control chromosomes in the GnomAD database, including 4,206 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 0.15 (4206 hom., cov: 32)
• Consequence: TP53 NM_000546.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TP53	NM_000546.6	c.-29+2689T>G		intron_variant		ENST00000269305.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TP53	ENST00000269305.9	c.-29+2689T>G		intron_variant		1	NM_000546.6	P1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23229 AN: 151794 Hom.: 4187 Cov.: 32

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0810

Gnomad ASJ AF: 0.0441

Gnomad EAS AF: 0.0212

Gnomad SAS AF: 0.0716

Gnomad FIN AF: 0.0144

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0433

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.153 AC: 23289 AN: 151912 Hom.: 4206 Cov.: 32 AF XY: 0.148 AC XY: 10971 AN XY: 74284

Gnomad4 AFR AF: 0.436

Gnomad4 AMR AF: 0.0809

Gnomad4 ASJ AF: 0.0441

Gnomad4 EAS AF: 0.0213

Gnomad4 SAS AF: 0.0725

Gnomad4 FIN AF: 0.0144

Gnomad4 NFE AF: 0.0433

Gnomad4 OTH AF: 0.132

Alfa AF: 0.0883 Hom.: 331

Bravo AF: 0.171

Asia WGS AF: 0.0640 AC: 222 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.0
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs9903378; hg19: chr17-7588006;