17-7674797-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.230

Publications

138 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: ClinGen, G2P, Labcorp Genetics (formerly Invitae), 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 -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000546.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TP53	NM_000546.6	MANE Select	c.672+62A>G	intron	N/A	NP_000537.3
TP53	NM_001126112.3		c.672+62A>G	intron	N/A	NP_001119584.1	K7PPA8
TP53	NM_001407262.1		c.672+62A>G	intron	N/A	NP_001394191.1	K7PPA8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TP53	ENST00000269305.9	TSL:1 MANE Select	c.672+62A>G	intron	N/A	ENSP00000269305.4	P04637-1
TP53	ENST00000445888.6	TSL:1	c.672+62A>G	intron	N/A	ENSP00000391478.2	P04637-1
TP53	ENST00000610292.4	TSL:1	c.555+62A>G	intron	N/A	ENSP00000478219.1	P04637-4

Frequencies

GnomAD3 genomes

AF:

0.831

AC:

126260

AN:

152020

Hom.:

52884

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.863

AC:

190495

AN:

220650

AF XY:

0.858

show subpopulations

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 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.:

AF XY:

0.864

AC XY:

555318

AN XY:

642662

show subpopulations

African (AFR)

AF:

0.709

AC:

20789

AN:

29324

American (AMR)

AF:

0.921

AC:

38155

AN:

41428

Ashkenazi Jewish (ASJ)

AF:

0.835

AC:

20622

AN:

24702

East Asian (EAS)

AF:

0.972

AC:

36750

AN:

37794

South Asian (SAS)

AF:

0.793

AC:

64187

AN:

80970

European-Finnish (FIN)

AF:

0.887

AC:

46417

AN:

52306

Middle Eastern (MID)

AF:

0.697

AC:

3776

AN:

5414

European-Non Finnish (NFE)

AF:

0.874

AC:

830256

AN:

950480

Other (OTH)

AF:

0.859

AC:

46634

AN:

54288

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

8270

16540

24809

33079

41349

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17122

34244

51366

68488

85610

<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:

0.830

AC:

126345

AN:

152140

Hom.:

52925

Cov.:

AF XY:

0.831

AC XY:

61789

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.713

AC:

29578

AN:

41484

American (AMR)

AF:

0.885

AC:

13511

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.840

AC:

2915

AN:

3470

East Asian (EAS)

AF:

0.966

AC:

5006

AN:

5180

South Asian (SAS)

AF:

0.799

AC:

3854

AN:

4826

European-Finnish (FIN)

AF:

0.890

AC:

9428

AN:

10594

Middle Eastern (MID)

AF:

0.690

AC:

203

AN:

294

European-Non Finnish (NFE)

AF:

0.873

AC:

59327

AN:

67992

Other (OTH)

AF:

0.834

AC:

1764

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1078

2156

3234

4312

5390

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

884

1768

2652

3536

4420

<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:

0.857

Hom.:

209371

Bravo

AF:

0.828

Asia WGS

AF:

0.887

AC:

3083

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Hereditary cancer-predisposing syndrome (1)

Li-Fraumeni syndrome 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.4

(source)

DANN

Benign

0.65

PhyloP100

0.23

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over