chr17-7674811-C-T

Variant names:

• chr17-7674811-C-T
• rs17884607
• NM_000546.6:c.672+48G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000546.6(TP53):​c.672+48G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000683 in 1,555,924 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00046 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00071 (11 hom.)
• Consequence: TP53 NM_000546.6 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.241
• Publications: 3 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 17-7674811-C-T is Benign according to our data. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7674811-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 1194751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00046 (70/152330) while in subpopulation SAS AF = 0.0141 (68/4834). AF 95% confidence interval is 0.0114. There are 2 homozygotes in GnomAd4. There are 50 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 70 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TP53	NM_000546.6	c.672+48G>A		intron_variant	Intron 6 of 10	ENST00000269305.9	NP_000537.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TP53	ENST00000269305.9	c.672+48G>A		intron_variant	Intron 6 of 10	1	NM_000546.6	ENSP00000269305.4

Frequencies

GnomAD3 genomes AF: 0.000466 AC: 71 AN: 152212 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0143

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00145 AC: 343 AN: 237332 AF XY: 0.00192

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000489

Gnomad NFE exome AF: 0.0000847

Gnomad OTH exome AF: 0.00119

GnomAD4 exome AF: 0.000707 AC: 992 AN: 1403594 Hom.: 11 Cov.: 27 AF XY: 0.00101 AC XY: 708 AN XY: 700864

African (AFR) AF: 0.0000623 AC: 2 AN: 32092

American (AMR) AF: 0.0000460 AC: 2 AN: 43460

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25642

East Asian (EAS) AF: 0.0000256 AC: 1 AN: 39072

South Asian (SAS) AF: 0.0106 AC: 892 AN: 84324

European-Finnish (FIN) AF: 0.0000377 AC: 2 AN: 53014

Middle Eastern (MID) AF: 0.000177 AC: 1 AN: 5650

European-Non Finnish (NFE) AF: 0.0000405 AC: 43 AN: 1061930

Other (OTH) AF: 0.000839 AC: 49 AN: 58410

GnomAD4 genome AF: 0.000460 AC: 70 AN: 152330 Hom.: 2 Cov.: 33 AF XY: 0.000671 AC XY: 50 AN XY: 74496

African (AFR) AF: 0.00 AC: 0 AN: 41568

American (AMR) AF: 0.0000654 AC: 1 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.0141 AC: 68 AN: 4834

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000164 Hom.: 0

Bravo AF: 0.000106

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TP53: BS1, BS2 -

Jul 22, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary cancer-predisposing syndrome Benign:2

Jun 18, 2022

Genome-Nilou Lab

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 13, 2021

Sema4, Sema4

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: curation

- -

not specified Benign:1

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Li-Fraumeni syndrome 1 Benign:1

Jun 18, 2022

Genome-Nilou Lab

Significance: Likely 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	-0.76
CADD	Benign	2.8
DANN	Benign	0.75
PhyloP100		-0.24
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs17884607; hg19: chr17-7578129;