rs1641549

Positions:

• chr17-7671457-C-T

Variant summary

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

The NM_000546.6(TP53):​c.994-742G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 151,960 control chromosomes in the GnomAD database, including 10,312 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 0.35 (10312 hom., cov: 32)
• Consequence: TP53 NM_000546.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TP53	NM_000546.6	c.994-742G>A		intron_variant		ENST00000269305.9	NP_000537.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TP53	ENST00000269305.9	c.994-742G>A		intron_variant		1	NM_000546.6	ENSP00000269305.4

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53178 AN: 151842 Hom.: 10277 Cov.: 32

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.351 AC: 53268 AN: 151960 Hom.: 10312 Cov.: 32 AF XY: 0.353 AC XY: 26175 AN XY: 74254

Gnomad4 AFR AF: 0.521

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.282

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.477

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.329

Alfa AF: 0.323 Hom.: 1071

Bravo AF: 0.356

Asia WGS AF: 0.477 AC: 1656 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.52
DANN	Benign	0.53

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: rs1641549; hg19: chr17-7574775; COSMIC: COSV53538718; COSMIC: COSV53538718;