Genetic Variant TP53:c.1101-221G>A (chr17-7669911-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000546.6(TP53):c.1101-221G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 151,812 control chromosomes in the GnomAD database, including 2,943 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.15 ( 2943 hom., cov: 32)

Consequence

TP53
NM_000546.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.811

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.02).

BP6

Variant 17-7669911-C-T is Benign according to our data. Variant chr17-7669911-C-T is described in ClinVar as [Benign]. Clinvar id is 1269356.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TP53	NM_000546.6 link	c.1101-221G>A		intron_variant	Intron 10 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.1101-221G>A		intron_variant	Intron 10 of 10	1	NM_000546.6	ENSP00000269305.4		P04637-1

Frequencies

GnomAD3 genomes

AF:

0.154

AC:

23296

AN:

151694

Hom.:

2931

Cov.:

show subpopulations

Gnomad AFR

AF:

0.348

Gnomad AMI

AF:

0.130

Gnomad AMR

AF:

0.0962

Gnomad ASJ

AF:

0.0598

Gnomad EAS

AF:

0.0712

Gnomad SAS

AF:

0.0915

Gnomad FIN

AF:

0.110

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0726

Gnomad OTH

AF:

0.118

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.154

AC:

23364

AN:

151812

Hom.:

2943

Cov.:

AF XY:

0.153

AC XY:

11328

AN XY:

74212

show subpopulations

African (AFR)

AF:

0.348

AC:

14400

AN:

41340

American (AMR)

AF:

0.0961

AC:

1464

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.0598

AC:

207

AN:

3462

East Asian (EAS)

AF:

0.0717

AC:

370

AN:

5160

South Asian (SAS)

AF:

0.0913

AC:

440

AN:

4818

European-Finnish (FIN)

AF:

0.110

AC:

1157

AN:

10550

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0726

AC:

4932

AN:

67932

Other (OTH)

AF:

0.125

AC:

263

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

879

1758

2636

3515

4394

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.125

Hom.:

274

Bravo

AF:

0.163

Asia WGS

AF:

0.154

AC:

537

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 24, 2018

GeneDx

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

-1.0

CADD

Benign

0.25

(source)

DANN

Benign

0.37

PhyloP100

-0.81

Mutation Taster

=6/94

disease causing

(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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chr17-7669911-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over