17-7674797-T-C

Position:

• chr17-7674797-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000546.6(TP53):​c.672+62A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.864 in 1,428,846 control chromosomes in the GnomAD database, including 534,669 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.83 (52925 hom., cov: 32)
  • Exomes 𝑓: 0.87 (481744 hom.)
• Consequence: TP53 NM_000546.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.230

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 17-7674797-T-C is Benign according to our data. Variant chr17-7674797-T-C is described in ClinVar as [Benign]. Clinvar id is 256603.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TP53	NM_000546.6	c.672+62A>G		intron_variant		ENST00000269305.9	NP_000537.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TP53	ENST00000269305.9	c.672+62A>G		intron_variant		1	NM_000546.6	ENSP00000269305	P1

Frequencies

GnomAD3 genomes AF: 0.831 AC: 126260 AN: 152020 Hom.: 52884 Cov.: 32

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.832

Gnomad AMR AF: 0.884

Gnomad ASJ AF: 0.840

Gnomad EAS AF: 0.967

Gnomad SAS AF: 0.799

Gnomad FIN AF: 0.890

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.873

Gnomad OTH AF: 0.833

GnomAD3 exomes AF: 0.863 AC: 190495 AN: 220650 Hom.: 82558 AF XY: 0.858 AC XY: 102250 AN XY: 119184

Gnomad AFR exome AF: 0.716

Gnomad AMR exome AF: 0.927

Gnomad ASJ exome AF: 0.832

Gnomad EAS exome AF: 0.966

Gnomad SAS exome AF: 0.793

Gnomad FIN exome AF: 0.883

Gnomad NFE exome AF: 0.867

Gnomad OTH exome AF: 0.853

GnomAD4 exome AF: 0.868 AC: 1107586 AN: 1276706 Hom.: 481744 Cov.: 18 AF XY: 0.864 AC XY: 555318 AN XY: 642662

Gnomad4 AFR exome AF: 0.709

Gnomad4 AMR exome AF: 0.921

Gnomad4 ASJ exome AF: 0.835

Gnomad4 EAS exome AF: 0.972

Gnomad4 SAS exome AF: 0.793

Gnomad4 FIN exome AF: 0.887

Gnomad4 NFE exome AF: 0.874

Gnomad4 OTH exome AF: 0.859

GnomAD4 genome AF: 0.830 AC: 126345 AN: 152140 Hom.: 52925 Cov.: 32 AF XY: 0.831 AC XY: 61789 AN XY: 74360

Gnomad4 AFR AF: 0.713

Gnomad4 AMR AF: 0.885

Gnomad4 ASJ AF: 0.840

Gnomad4 EAS AF: 0.966

Gnomad4 SAS AF: 0.799

Gnomad4 FIN AF: 0.890

Gnomad4 NFE AF: 0.873

Gnomad4 OTH AF: 0.834

Alfa AF: 0.861 Hom.: 91532

Bravo AF: 0.828

Asia WGS AF: 0.887 AC: 3083 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Jul 02, 2018	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Li-Fraumeni syndrome 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jun 18, 2022

- -

Hereditary cancer-predisposing syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jun 18, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1625895; hg19: chr17-7578115;