17-7676443-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000610292.4(TP53):c.-83G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000266 in 1,613,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

TP53
ENST00000610292.4 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.202

Publications

3 publications found

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 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

TP53 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 17-7676443-C-T is Benign according to our data. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7676443-C-T is described in CliVar as Likely_benign. Clinvar id is 492605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TP53	NM_000546.6 link	c.75-40G>A		intron_variant	Intron 2 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.75-40G>A		intron_variant	Intron 2 of 10	1	NM_000546.6	ENSP00000269305.4		P04637-1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

151980

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000480

GnomAD2 exomes

AF:

0.0000362

AC:

AN:

248334

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000268

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000239

AC:

AN:

1461504

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727036

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.000112

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53164

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000252

AC:

AN:

1111890

Other (OTH)

AF:

0.0000331

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152094

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41474

American (AMR)

AF:

0.000196

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

67992

Other (OTH)

AF:

0.000475

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000529

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary cancer-predisposing syndrome

Benign:1

Dec 09, 2015

Color Diagnostics, LLC DBA Color Health

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

-0.95

CADD

Benign

5.8

(source)

DANN

Benign

0.59

PhyloP100

-0.20

PromoterAI

-0.044

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over