chr17-7675361-A-G

Variant names:

Variant summary

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

The ENST00000504937.5(TP53):c.-146T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0604 in 1,527,276 control chromosomes in the GnomAD database, including 3,122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.073 ( 500 hom., cov: 31)

Exomes 𝑓: 0.059 ( 2622 hom. )

Consequence

TP53
ENST00000504937.5 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.545

Publications

40 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=-0.9).

BP6

Variant 17-7675361-A-G is Benign according to our data. Variant chr17-7675361-A-G is described in ClinVar as Benign. ClinVar VariationId is 1245512.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000504937.5. 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.376-125T>C	intron	N/A	NP_000537.3
TP53	NM_001126112.3		c.376-125T>C	intron	N/A	NP_001119584.1	K7PPA8
TP53	NM_001407262.1		c.376-125T>C	intron	N/A	NP_001394191.1	K7PPA8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TP53	ENST00000504937.5	TSL:1	c.-146T>C	5_prime_UTR	Exon 1 of 7	ENSP00000481179.1	P04637-7
TP53	ENST00000619186.4	TSL:1	c.-227T>C	5_prime_UTR	Exon 1 of 7	ENSP00000484375.1	A0A087X1Q1
TP53	ENST00000504290.5	TSL:1	c.-146T>C	5_prime_UTR	Exon 1 of 8	ENSP00000484409.1	P04637-9

Frequencies

GnomAD3 genomes

AF:

0.0729

AC:

11008

AN:

150918

Hom.:

496

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.105

Gnomad AMR

AF:

0.0552

Gnomad ASJ

AF:

0.0510

Gnomad EAS

AF:

0.0723

Gnomad SAS

AF:

0.0741

Gnomad FIN

AF:

0.105

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.0547

Gnomad OTH

AF:

0.0588

GnomAD4 exome

AF:

0.0590

AC:

81165

AN:

1376250

Hom.:

2622

Cov.:

AF XY:

0.0593

AC XY:

40278

AN XY:

679330

show subpopulations

African (AFR)

AF:

0.104

AC:

3249

AN:

31140

American (AMR)

AF:

0.0547

AC:

1875

AN:

34276

Ashkenazi Jewish (ASJ)

AF:

0.0474

AC:

1164

AN:

24532

East Asian (EAS)

AF:

0.0693

AC:

2473

AN:

35706

South Asian (SAS)

AF:

0.0798

AC:

6203

AN:

77750

European-Finnish (FIN)

AF:

0.101

AC:

3610

AN:

35760

Middle Eastern (MID)

AF:

0.0205

AC:

AN:

4150

European-Non Finnish (NFE)

AF:

0.0550

AC:

59104

AN:

1075522

Other (OTH)

AF:

0.0593

AC:

3402

AN:

57414

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

3404

6808

10213

13617

17021

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2344

4688

7032

9376

11720

<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:

0.0731

AC:

11043

AN:

151026

Hom.:

500

Cov.:

AF XY:

0.0748

AC XY:

5508

AN XY:

73676

show subpopulations

African (AFR)

AF:

0.104

AC:

4275

AN:

41104

American (AMR)

AF:

0.0554

AC:

835

AN:

15060

Ashkenazi Jewish (ASJ)

AF:

0.0510

AC:

177

AN:

3472

East Asian (EAS)

AF:

0.0729

AC:

373

AN:

5118

South Asian (SAS)

AF:

0.0740

AC:

355

AN:

4796

European-Finnish (FIN)

AF:

0.105

AC:

1079

AN:

10300

Middle Eastern (MID)

AF:

0.0103

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0547

AC:

3711

AN:

67876

Other (OTH)

AF:

0.0663

AC:

139

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

509

1018

1527

2036

2545

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

130

260

390

520

650

<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:

0.0627

Hom.:

449

Bravo

AF:

0.0723

Asia WGS

AF:

0.126

AC:

436

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.47

(source)

DANN

Benign

0.57

PhyloP100

0.55

PromoterAI

-0.0031

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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