rs1642785

Variant names:

• chr17-7676483-G-C
• rs1642785
• ENST00000610292.4:c.-123C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-7676483-G-C
• chr17-7676483-G-T
• chr17-7676483-G-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001126118.2(TP53):​c.-123C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 1,591,856 control chromosomes in the GnomAD database, including 397,543 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.66 (33859 hom., cov: 29)
  • Exomes 𝑓: 0.71 (363684 hom.)
• Consequence: TP53 NM_001126118.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:14
• Conservation: PhyloP100: 0.128
• Publications: 90 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 17-7676483-G-C is Benign according to our data. Variant chr17-7676483-G-C is described in ClinVar as Benign. ClinVar VariationId is 137691.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001126118.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TP53	NM_000546.6	MANE Select	c.74+38C>G		intron	N/A	NP_000537.3
	TP53	NM_001126118.2		c.-123C>G		5_prime_UTR	Exon 2 of 10	NP_001119590.1	H2EHT1
	TP53	NM_001126112.3		c.74+38C>G		intron	N/A	NP_001119584.1	K7PPA8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TP53	ENST00000610292.4	TSL:1	c.-123C>G		5_prime_UTR	Exon 2 of 10	ENSP00000478219.1	P04637-4
	TP53	ENST00000269305.9	TSL:1 MANE Select	c.74+38C>G		intron	N/A	ENSP00000269305.4	P04637-1
	TP53	ENST00000445888.6	TSL:1	c.74+38C>G		intron	N/A	ENSP00000391478.2	P04637-1

Frequencies

GnomAD3 genomes AF: 0.660 AC: 100053 AN: 151570 Hom.: 33859 Cov.: 29

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.710

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.726

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.685

GnomAD2 exomes AF: 0.673 AC: 166700 AN: 247548 AF XY: 0.667

Gnomad AFR exome AF: 0.516

Gnomad AMR exome AF: 0.718

Gnomad ASJ exome AF: 0.710

Gnomad EAS exome AF: 0.571

Gnomad FIN exome AF: 0.719

Gnomad NFE exome AF: 0.732

Gnomad OTH exome AF: 0.694

GnomAD4 exome AF: 0.708 AC: 1020340 AN: 1440172 Hom.: 363684 Cov.: 43 AF XY: 0.703 AC XY: 503952 AN XY: 717364

African (AFR) AF: 0.503 AC: 16760 AN: 33294

American (AMR) AF: 0.719 AC: 32091 AN: 44644

Ashkenazi Jewish (ASJ) AF: 0.712 AC: 18519 AN: 26012

East Asian (EAS) AF: 0.604 AC: 23952 AN: 39624

South Asian (SAS) AF: 0.504 AC: 43370 AN: 86008

European-Finnish (FIN) AF: 0.723 AC: 38374 AN: 53088

Middle Eastern (MID) AF: 0.603 AC: 3455 AN: 5728

European-Non Finnish (NFE) AF: 0.735 AC: 802203 AN: 1092010

Other (OTH) AF: 0.696 AC: 41616 AN: 59764

GnomAD4 genome AF: 0.660 AC: 100079 AN: 151684 Hom.: 33859 Cov.: 29 AF XY: 0.656 AC XY: 48622 AN XY: 74104

African (AFR) AF: 0.515 AC: 21280 AN: 41348

American (AMR) AF: 0.711 AC: 10807 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 2482 AN: 3470

East Asian (EAS) AF: 0.573 AC: 2931 AN: 5116

South Asian (SAS) AF: 0.521 AC: 2507 AN: 4812

European-Finnish (FIN) AF: 0.726 AC: 7622 AN: 10498

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.740 AC: 50235 AN: 67928

Other (OTH) AF: 0.676 AC: 1420 AN: 2100

Alfa AF: 0.688 Hom.: 6716

Bravo AF: 0.656

Asia WGS AF: 0.526 AC: 1831 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	3	Hereditary cancer-predisposing syndrome (3)
-	-	2	Li-Fraumeni syndrome 1 (2)
-	-	2	not provided (2)
-	-	1	Hereditary breast ovarian cancer syndrome (1)
-	-	1	Li-Fraumeni syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.2
DANN	Benign	0.57
PhyloP100		0.13
PromoterAI		-0.070	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1642785; hg19: chr17-7579801; COSMIC: COSV52668860; COSMIC: COSV52668860;