17-7674326-C-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000546.6(TP53):c.673-36G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0155 in 1,303,868 control chromosomes in the GnomAD database, including 223 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 17 hom., cov: 30)

Exomes 𝑓: 0.016 ( 206 hom. )

Consequence

TP53
NM_000546.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -1.50

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 17-7674326-C-G is Benign according to our data. Variant chr17-7674326-C-G is described in ClinVar as [Benign]. Clinvar id is 221184.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674326-C-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0117 (1760/150704) while in subpopulation NFE AF= 0.0193 (1308/67818). AF 95% confidence interval is 0.0184. There are 17 homozygotes in gnomad4. There are 815 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1760 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TP53	NM_000546.6 link	c.673-36G>C		intron_variant	Intron 6 of 10	ENST00000269305.9	NP_000537.3	P04637-1K7PPA8Q53GA5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TP53	ENST00000269305.9 link	c.673-36G>C		intron_variant	Intron 6 of 10	1	NM_000546.6	ENSP00000269305.4		P04637-1

Frequencies

GnomAD3 genomes

AF:

0.0117

AC:

1760

AN:

150688

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00268

Gnomad AMI

AF:

0.0286

Gnomad AMR

AF:

0.00970

Gnomad ASJ

AF:

0.0145

Gnomad EAS

AF:

0.000390

Gnomad SAS

AF:

0.00524

Gnomad FIN

AF:

0.00539

Gnomad MID

AF:

0.0392

Gnomad NFE

AF:

0.0193

Gnomad OTH

AF:

0.0131

GnomAD3 exomes

AF:

0.0122

AC:

3054

AN:

250078

Hom.:

AF XY:

0.0126

AC XY:

1710

AN XY:

135202

show subpopulations

Gnomad AFR exome

AF:

0.00247

Gnomad AMR exome

AF:

0.00709

Gnomad ASJ exome

AF:

0.0166

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00412

Gnomad FIN exome

AF:

0.00452

Gnomad NFE exome

AF:

0.0202

Gnomad OTH exome

AF:

0.0149

GnomAD4 exome

AF:

0.0160

AC:

18466

AN:

1153164

Hom.:

206

Cov.:

AF XY:

0.0158

AC XY:

9282

AN XY:

587594

show subpopulations

Gnomad4 AFR exome

AF:

0.00291

Gnomad4 AMR exome

AF:

0.00760

Gnomad4 ASJ exome

AF:

0.0158

Gnomad4 EAS exome

AF:

0.0000525

Gnomad4 SAS exome

AF:

0.00482

Gnomad4 FIN exome

AF:

0.00542

Gnomad4 NFE exome

AF:

0.0192

Gnomad4 OTH exome

AF:

0.0166

GnomAD4 genome

AF:

0.0117

AC:

1760

AN:

150704

Hom.:

Cov.:

AF XY:

0.0111

AC XY:

815

AN XY:

73432

show subpopulations

Gnomad4 AFR

AF:

0.00268

Gnomad4 AMR

AF:

0.00969

Gnomad4 ASJ

AF:

0.0145

Gnomad4 EAS

AF:

0.000391

Gnomad4 SAS

AF:

0.00526

Gnomad4 FIN

AF:

0.00539

Gnomad4 NFE

AF:

0.0193

Gnomad4 OTH

AF:

0.0130

Alfa

AF:

0.00774

Hom.:

Bravo

AF:

0.0113

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Li-Fraumeni syndrome 1

Benign:3

Jun 18, 2022

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 05, 2016

Counsyl

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 04, 2015

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:3

Oct 09, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 10706125) -

not specified

Benign:2

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary cancer-predisposing syndrome

Benign:2

Nov 18, 2014

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Jun 18, 2022

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Li-Fraumeni syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary breast ovarian cancer syndrome

Benign:1

Apr 19, 2022

National Health Laboratory Service, Universitas Academic Hospital and University of the Free State

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

-0.91

CADD

Benign

0.017

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over