rs6503048

Positions:

• chr17-7669911-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.811

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
TP53	NM_000546.6	c.1101-221G>A		intron_variant		ENST00000269305.9	NP_000537.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TP53	ENST00000269305.9	c.1101-221G>A		intron_variant		1	NM_000546.6	ENSP00000269305	P1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23296 AN: 151694 Hom.: 2931 Cov.: 32

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.: 32 AF XY: 0.153 AC XY: 11328 AN XY: 74212

Gnomad4 AFR AF: 0.348

Gnomad4 AMR AF: 0.0961

Gnomad4 ASJ AF: 0.0598

Gnomad4 EAS AF: 0.0717

Gnomad4 SAS AF: 0.0913

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.0726

Gnomad4 OTH AF: 0.125

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

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.25
DANN	Benign	0.37

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

LitVar

Other links and lift over

dbSNP: rs6503048; hg19: chr17-7573229; COSMIC: COSV53538708; COSMIC: COSV53538708;