About TP53
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
TP53 c.215C>G, p.(Pro72Arg)
Classification
Benign
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is benign. Select a step to read what it means.
Benign.A benign classification under the recorded framework.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
LYFE Sciences is an AI system, and it can make mistakes.
Criteria may be applied incorrectly, sources may be misread, and a
confident-looking classification can still be wrong.
Double-check every criterion and its underlying evidence
before relying on any call.
01The reasoning
How it was classified
The recorded framework is ClinGen TP53 VCEP v2.4.0. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
Recorded applied criteria
The applied criteria and their strengths are shown as assessed under the stated framework.
Pathogenic evidence criteria: 0
Benign evidence criteria: 2
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 2
BA1Stand alone
BA1 · stand alone
This variant exceeds the TP53 VCEP BA1 stand-alone benign threshold by a wide margin. In gnomAD v4.1 the highest observed filtering allele frequency is 0.746273 and in gnomAD v2.1 it is 0.733613, whereas BA1 requires a filtering allele frequency of at least 0.001 in a qualifying ancestry group.
BP4Moderate
BP4 · moderate
TP53 VCEP in silico evidence supports a benign interpretation. In the TP53 PP3/BP4 worksheet, c.215C>G is assigned BP4_moderate with BayesDel -0.108475, which is below the BP4_moderate threshold of -0.008, and SpliceAI predicts no significant splice impact with a maximum delta score of 0.05, which is below the no-splicing-impact threshold of 0.2.
Recorded classification: Benign
Tavtigian et.al., 2020 - Bayesian adaptation of Richards et.al., 2015 v2.4.0 point-based framework: BA1 stand-alone benign (-8) + BP4 moderate (-2) = -10 points, which maps to Benign.
02The sources
Evidence at a glance
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1
gnomAD v2.1
Population frequency
1,142,226 / 1,613,582 alleles
gnomAD v4.1: 1,142,226 / 1,613,582 alleles. Recorded AF 0.707882. Recorded homozygote count 411964.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.662887; MAF= 66.28868%, 186832/281846 alleles, homozygotes = 63926) and has highest observed frequency in the European (non-Finnish) population (AF= 0.73659; MAF= 73.65900%, 94889/128822 alleles, homozygotes = 34940); grpmax FAF= 0.733613.
No screenshot for this evidence
Computational predictions
Not recorded
No SpliceAI or REVEL score is recorded in the fields used for this tile.
ClinVar submissions
Not recorded
A ClinVar laboratory submission summary was not recorded.
Context only
ClinVar ↗
Functional evidence
Statement recorded
OncoKB has not reviewed this specific variant; no variant-level oncogenicity or biological effect is available. Gene-level context: TP53, a tumor suppressor in the DNA damage pathway, is the most frequently mutated gene in cancer.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
Not assessed
No COSMIC evidence statement is recorded in this case.
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under ClinGen TP53 VCEP v2.4.0, with the data and sources behind each one.
28 criteria with recorded statuses: 2 met · 6 not met · 8 not assessed · 12 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
The TP53 c.215C>G (p.Pro72Arg, p.P72R) variant has not been observed in COSMIC as a recurrent somatic cancer variant and is reported in ClinVar as benign, including a benign ClinGen TP53 Variant Curation Expert Panel classification.
This variant is very common in population databases, with gnomAD v4.1 total allele frequency 0.707882 and grpmax filtering allele frequency 0.746273, far above the TP53 BA1 benign threshold of 0.001.
Available studies of the common TP53 codon 72 polymorphism describe biologic differences between alleles, but no TP53 VCEP-eligible functional code assignment for p.Pro72Arg was identified in the TP53 functional worksheet.
TP53 VCEP in silico data support a benign interpretation because c.215C>G is assigned BP4_moderate in the TP53 PP3/BP4 worksheet with BayesDel -0.108475, and SpliceAI predicts no significant splice effect with a maximum delta score of 0.05.
No criteria match.
Met · 2
BA1 Stand aloneThis variant exceeds the TP53 VCEP BA1 stand-alone benign threshold by a wide margin. In gnomAD v4.1 the highest observed filtering allele frequency is 0.746273 and in gnomAD v2.1 it is 0.733613, whereas BA1 requires a filtering allele frequency of at least 0.001 in a qualifying ancestry group. Details ▾Hide ▴
Rule
TP53 VCEP BA1: FAF >=0.001 in a qualifying ancestry group.
Evidence considered
- gnomAD v4.1 grpmax FAF 0.746273.
- gnomAD v2.1 grpmax FAF 0.733613.
Sources
BP4 ModerateTP53 VCEP in silico evidence supports a benign interpretation. In the TP53 PP3/BP4 worksheet, c.215C>G is assigned BP4_moderate with BayesDel -0.108475, which is below the BP4_moderate threshold of -0.008, and SpliceAI predicts no significant splice impact with a maximum delta score of 0.05, which is below the no-splicing-impact threshold of 0.2. Details ▾Hide ▴
Rule
TP53 VCEP BP4_Moderate for missense variants: BayesDel <= -0.008 and no predicted splice impact with SpliceAI <0.2.
Evidence considered
- TP53 PP3-BP4 worksheet row for c.215C>G: Class C0
- BayesDel -0.108475
- BP4_moderate.
- SpliceAI max delta score 0.05.
Sources
vcep_p_p_3___b_p_4___c_o_d_e_sspliceai ↗vcep_f_l_o_w_c_h_a_r_t___f_o_r___a_p_p_l_i_c_a_t_i_o_n___o_f___p_p_3___2_c___b_p_4___2_c___a_n_d___b_p_7cspec ↗
Not met · 6 · evaluated, threshold not reached
PS3 Available publications describe biologic differences between codon 72 alleles, but no TP53 VCEP-eligible functional assignment showing non-functional or loss-of-function behavior for p.Pro72Arg was identified, so PS3 is not met. Details ▾Hide ▴
Rule
TP53 VCEP PS3 requires non-functional or partially functional assay evidence meeting the expert panel framework.
Evidence considered
- The TP53 Functional-worksheet did not provide a pre-assigned PS3 code for p.Pro72Arg.
- Reviewed literature discusses codon 72 polymorphism effects but does not establish TP53 VCEP-defined non-functional behavior for this variant.
Sources
vcep_f_u_n_c_t_i_o_n_a_l___w_o_r_k_s_h_e_e_tvcep_f_l_o_w_c_h_a_r_t___f_o_r___a_p_p_l_i_c_a_t_i_o_n___o_f___f_u_n_c_t_i_o_n_a_l___r_u_l_e___c_o_d_e_sPMID:10802655 ↗PMID:12567188 ↗PMID:16964264 ↗
PS4 Available evidence does not show enrichment of this variant in individuals with TP53-related disease. The variant is extremely common in population databases and is classified as benign by the ClinGen TP53 expert panel, so PS4 is not met. Details ▾Hide ▴
Rule
TP53 VCEP PS4 requires qualifying proband point accumulation after PM2_Supporting is satisfied; the observed population frequency is far above PM2 thresholds.
Evidence considered
- ClinVar lists a TP53 expert panel benign classification.
- gnomAD shows very high population frequency.
- COSMIC did not identify this variant as a recurrent somatic cancer variant.
Sources
PM1 This variant is not located in a TP53 mutational hotspot supported by the TP53 VCEP PM1 rules, and no significant hotspot row was identified for p.Pro72Arg. Details ▾Hide ▴
Rule
TP53 VCEP PM1 applies to specified hotspot codons or exact amino acid changes with enough somatic occurrences; those conditions were not met.
Evidence considered
- Cancer Hotspots review found no hotspot row for residue P72.
- TP53 VCEP PM1 moderate codons are 175
- 245
- 248
- 249
- 273
- and 282
- or variants with sufficient exact somatic counts.
Sources
PM2 Population frequency is far above the TP53 VCEP PM2 threshold. In gnomAD v4.1 the total allele frequency is 0.707882 and the highest observed population frequency is 0.747582, whereas PM2 requires a total frequency below 0.00003 and below 0.00004 within any ancestry group with multiple alleles. Details ▾Hide ▴
Rule
TP53 VCEP PM2_Supporting requires AF <0.00003 overall and <0.00004 in any relevant ancestry group.
Evidence considered
- gnomAD v4.1 total AF 0.707882
- European non-Finnish AF 0.747582.
- gnomAD v2.1 total AF 0.662887
- European non-Finnish AF 0.736590.
Sources
PP3 TP53 VCEP in silico data do not support a damaging effect. In the TP53 PP3/BP4 worksheet, c.215C>G is assigned BP4_moderate with BayesDel -0.108475, and SpliceAI predicts no significant splice impact with a maximum delta score of 0.05, so PP3 is not met. Details ▾Hide ▴
Rule
TP53 VCEP PP3 for missense variants requires qualifying damaging aGVGD/BayesDel results; this variant instead has a pre-assigned BP4_moderate call.
Evidence considered
- TP53 PP3-BP4 worksheet row for c.215C>G: Class C0
- BayesDel -0.108475
- BP4_moderate.
- SpliceAI max delta score 0.05.
Sources
vcep_p_p_3___b_p_4___c_o_d_e_sspliceai ↗vcep_f_l_o_w_c_h_a_r_t___f_o_r___a_p_p_l_i_c_a_t_i_o_n___o_f___p_p_3___2_c___b_p_4___2_c___a_n_d___b_p_7cspec ↗
BS3 Available publications describe functional differences between codon 72 alleles, but no TP53 VCEP-eligible functional assignment showing retained function for p.Pro72Arg was identified in the TP53 functional worksheet, so BS3 is not met. Details ▾Hide ▴
Rule
TP53 VCEP BS3 requires functional or partially functional assay evidence meeting expert panel criteria.
Evidence considered
- The TP53 Functional-worksheet did not provide a pre-assigned BS3 code for p.Pro72Arg.
- Reviewed literature addresses a common codon 72 polymorphism but does not provide a TP53 VCEP benign functional code assignment for this specific variant.
Sources
vcep_f_u_n_c_t_i_o_n_a_l___w_o_r_k_s_h_e_e_tvcep_f_l_o_w_c_h_a_r_t___f_o_r___a_p_p_l_i_c_a_t_i_o_n___o_f___f_u_n_c_t_i_o_n_a_l___r_u_l_e___c_o_d_e_sPMID:10802655 ↗PMID:12567188 ↗PMID:16199549 ↗PMID:17535973 ↗PMID:17638920 ↗PMID:19521721 ↗PMID:21619694 ↗
Not assessed · 8 · no assessment recorded
PS1 No evidence was identified in the reviewed sources showing that this nucleotide change creates the same amino acid substitution as a TP53 variant previously classified as pathogenic or likely pathogenic under TP53 VCEP rules. Details ▾Hide ▴
Rule
TP53 VCEP PS1 applies only when the same amino acid change has already been classified as pathogenic or likely pathogenic.
Evidence considered
- TP53 VCEP PS1 requires the same amino acid change as a previously classified pathogenic or likely pathogenic TP53 variant.
- ClinVar shows this specific variant is classified as benign by the TP53 expert panel.
Still missing
- Residue-specific review of previously classified TP53 variants at codon 72 was not available in the reviewed sources.
Sources
PS2 No confirmed de novo observations were identified for this variant, so PS2 cannot be applied. Details ▾Hide ▴
Rule
TP53 VCEP PS2 requires de novo point accumulation; no qualifying observations were identified.
Evidence considered
- TP53 VCEP PS2 is point based and requires documented de novo observations in probands with Li-Fraumeni spectrum cancers.
Still missing
- No parental testing or de novo case data were identified.
Sources
cspec ↗vcep_t_a_b_l_e___o_f___l_f_s___c_a_n_c_e_r_s___a_n_d___p_o_i_n_t_s___f_o_r___p_s_2___a_n_d___p_p_1___c_o_d_e___a_p_p_l_i_c_a_t_i_o_n
PM5 No reviewed source established that other missense variants at codon 72 have been previously classified as pathogenic or likely pathogenic under TP53 VCEP rules, so PM5 was not applied. Details ▾Hide ▴
Rule
TP53 VCEP PM5 requires previously classified pathogenic or likely pathogenic missense variants at the same residue.
Evidence considered
- TP53 VCEP PM5 depends on prior TP53 VCEP classifications at the same residue.
- ClinVar shows the current variant itself is classified as benign by the TP53 expert panel.
Still missing
- A residue-specific TP53 VCEP review for alternative missense changes at codon 72 was not available in the reviewed sources.
Sources
PP1 No segregation data were identified for this variant, so PP1 cannot be applied. Details ▾Hide ▴
Rule
TP53 VCEP PP1 is point/meiosis based; no qualifying segregation observations were identified.
Evidence considered
- TP53 VCEP PP1 requires 3 or more informative meioses with cosegregation.
Still missing
- No informative family cosegregation data were identified.
Sources
cspec ↗vcep_t_a_b_l_e___o_f___l_f_s___c_a_n_c_e_r_s___a_n_d___p_o_i_n_t_s___f_o_r___p_s_2___a_n_d___p_p_1___c_o_d_e___a_p_p_l_i_c_a_t_i_o_n
PP4 No qualifying low-variant-allele-fraction observation was identified, so the TP53-specific PP4 criterion was not applied. Details ▾Hide ▴
Rule
TP53 VCEP PP4 requires qualifying VAF observations.
Evidence considered
- TP53 VCEP PP4 is based on specific VAF observations rather than phenotype alone.
Still missing
- No blood or tissue variant allele fraction data consistent with the TP53 PP4 mosaicism framework were identified.
Sources
BS1 Population frequency is far above the BS1 threshold, but BA1 is already met at stand-alone strength, so BS1 was not additionally applied to avoid double counting the same population evidence. Details ▾Hide ▴
Rule
TP53 VCEP BS1: FAF >=0.0003 and <0.001; not additionally applied when BA1 is already satisfied.
Evidence considered
- gnomAD v4.1 grpmax FAF 0.746273.
- gnomAD v2.1 grpmax FAF 0.733613.
- BA1 threshold is already exceeded by a wide margin.
Sources
BS2 No single-source series of unaffected older female carriers was identified, so BS2 cannot be applied. Details ▾Hide ▴
Rule
TP53 VCEP BS2 requires 2 or more qualifying unaffected female carriers from one source.
Evidence considered
- TP53 VCEP BS2 requires unrelated females aged 60 years or older without cancer from a single source.
Still missing
- No qualifying unaffected-carrier dataset meeting TP53 VCEP BS2 requirements was identified.
Sources
BS4 No family data showing lack of segregation with Li-Fraumeni spectrum cancers were identified, so BS4 cannot be applied. Details ▾Hide ▴
Rule
TP53 VCEP BS4 requires informative non-segregation data.
Evidence considered
- TP53 VCEP BS4 requires lack of segregation in affected relatives with LFS-associated cancers.
Still missing
- No informative non-segregation data were identified.
Sources
cspec ↗vcep_t_a_b_l_e___o_f___l_f_s___c_a_n_c_e_r_s___a_n_d___p_o_i_n_t_s___f_o_r___p_s_2___a_n_d___p_p_1___c_o_d_e___a_p_p_l_i_c_a_t_i_o_n
Not applicable · 12· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/AThis missense variant does not create a predicted null allele and is not a canonical +/-1,2 splice-site change, so PVS1 does not apply. Details ▾Hide ▴
Evidence considered
- Variant-level PVS1 assessment categorized this change outside the null-variant buckets used for PVS1.
- TP53 VCEP PVS1 guidance is limited to null and qualifying splice variants.
Sources
pvs1_variant_assessmentcspec ↗
PM3 N/APM3 is not applicable in the TP53 VCEP framework for this disorder context. Details ▾Hide ▴
PM4 N/APM4 is not applicable because this is not a protein length-changing variant and TP53 VCEP does not use PM4 in this context. Details ▾Hide ▴
PM6 N/APM6 is not applicable in the TP53 VCEP framework. Details ▾Hide ▴
PP2 N/APP2 is not applicable in the TP53 VCEP framework. Details ▾Hide ▴
PP5 N/APP5 is not applicable in the TP53 VCEP framework. Details ▾Hide ▴
BP1 N/ABP1 is not applicable in the TP53 VCEP framework. Details ▾Hide ▴
BP2 N/ABP2 is not applicable in the TP53 VCEP framework. Details ▾Hide ▴
BP3 N/ABP3 is not applicable in the TP53 VCEP framework. Details ▾Hide ▴
BP5 N/ABP5 is not applicable in the TP53 VCEP framework. Details ▾Hide ▴
BP6 N/ABP6 is not applicable in the TP53 VCEP framework. Details ▾Hide ▴
BP7 N/ABP7 does not apply because this is a missense variant rather than a synonymous or qualifying intronic variant. Details ▾Hide ▴
Evidence considered
- TP53 VCEP BP7 is limited to synonymous and certain intronic variants.
Sources
cspec ↗vcep_f_l_o_w_c_h_a_r_t___f_o_r___a_p_p_l_i_c_a_t_i_o_n___o_f___p_p_3___2_c___b_p_4___2_c___a_n_d___b_p_7
Identifiers
- Gene
- TP53
- Transcript
- NM_000546.5
- Coding (HGVS c.)
- NM_000546.5:c.215C>G
- Protein (HGVS p.)
- NP_000537.3:p.(Pro72Arg)
- GRCh38
- chr17:7676154 G>C
- GRCh37
- chr17:7579472 G>C
Gene diagram
Every interpreted variant in TP53, mapped onto the exon structure of NM_000546.5. Select a row to find it on the plot.
TP53NM_000546.5
Fetching transcript structure from UCSC…
Exons
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Transcript span
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Strand
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Variants mapped
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Source
UCSC ncbiRefSeqCurated
All variants in TP53
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Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
1,142,226 / 1,613,582 alleles
AF 0.708 · 411964 homozygotes · FAF 0.746
gnomAD v2.1
186,832 / 281,846 alleles
AF 0.663 · 63926 homozygotes · FAF 0.734
By genetic ancestry
gnomAD v4.1
AF 0.71 · 1142226 / 1,613,582 alleles · 411964 hom · FAF 0.75
| European (non-Finnish)882123 / 1,179,968 | 0.75329809 hom |
| European (Finnish)46913 / 63,994 | 0.7317252 hom |
| Ashkenazi Jewish21300 / 29,604 | 0.727644 hom |
| Admixed American42617 / 59,976 | 0.7115147 hom |
| Remaining individuals43349 / 62,476 | 0.6915169 hom |
| Amish611 / 912 | 0.67207 hom |
| Middle Eastern3519 / 5,810 | 0.611103 hom |
| East Asian26984 / 44,862 | 0.68137 hom |
| South Asian46205 / 91,050 | 0.5112001 hom |
| African/African American28605 / 74,930 | 0.385495 hom |
gnomAD v2.1
AF 0.66 · 186832 / 281,846 alleles · 63926 hom · FAF 0.73
| European (non-Finnish)94889 / 128,822 | 0.7434940 hom |
| European (Finnish)18300 / 25,100 | 0.736645 hom |
| Ashkenazi Jewish7414 / 10,366 | 0.722641 hom |
| Admixed American25286 / 35,416 | 0.719030 hom |
| Remaining individuals4999 / 7,178 | 0.71753 hom |
| East Asian11314 / 19,918 | 0.573235 hom |
| South Asian15313 / 30,614 | 0.53897 hom |
| African/African American9317 / 24,432 | 0.381785 hom |
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.707882; MAF= 70.78822%, 1142226/1613582 alleles, homozygotes = 411964) and has highest observed frequency in the European (non-Finnish) population (AF= 0.747582; MAF= 74.75821%, 882123/1179968 alleles, homozygotes = 329809); grpmax FAF= 0.746273.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.662887; MAF= 66.28868%, 186832/281846 alleles, homozygotes = 63926) and has highest observed frequency in the European (non-Finnish) population (AF= 0.73659; MAF= 73.65900%, 94889/128822 alleles, homozygotes = 34940); grpmax FAF= 0.733613.
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
BP4 ModerateTP53 VCEP in silico evidence supports a benign interpretation. In the TP53 PP3/BP4 worksheet, c.215C>G is assigned BP4_moderate with BayesDel -0.108475, which is below the BP4_moderate threshold of -0.008, and SpliceAI predicts no significant splice impact with a maximum delta score of 0.05, which is below the no-splicing-impact threshold of 0.2. Details ▾Hide ▴
Rule
TP53 VCEP BP4_Moderate for missense variants: BayesDel <= -0.008 and no predicted splice impact with SpliceAI <0.2.
Evidence considered
- TP53 PP3-BP4 worksheet row for c.215C>G: Class C0
- BayesDel -0.108475
- BP4_moderate.
- SpliceAI max delta score 0.05.
Sources
vcep_p_p_3___b_p_4___c_o_d_e_sspliceai ↗vcep_f_l_o_w_c_h_a_r_t___f_o_r___a_p_p_l_i_c_a_t_i_o_n___o_f___p_p_3___2_c___b_p_4___2_c___a_n_d___b_p_7cspec ↗
PP3 TP53 VCEP in silico data do not support a damaging effect. In the TP53 PP3/BP4 worksheet, c.215C>G is assigned BP4_moderate with BayesDel -0.108475, and SpliceAI predicts no significant splice impact with a maximum delta score of 0.05, so PP3 is not met. Details ▾Hide ▴
Rule
TP53 VCEP PP3 for missense variants requires qualifying damaging aGVGD/BayesDel results; this variant instead has a pre-assigned BP4_moderate call.
Evidence considered
- TP53 PP3-BP4 worksheet row for c.215C>G: Class C0
- BayesDel -0.108475
- BP4_moderate.
- SpliceAI max delta score 0.05.
Sources
vcep_p_p_3___b_p_4___c_o_d_e_sspliceai ↗vcep_f_l_o_w_c_h_a_r_t___f_o_r___a_p_p_l_i_c_a_t_i_o_n___o_f___p_p_3___2_c___b_p_4___2_c___a_n_d___b_p_7cspec ↗
BP7 N/ABP7 does not apply because this is a missense variant rather than a synonymous or qualifying intronic variant. Details ▾Hide ▴
Evidence considered
- TP53 VCEP BP7 is limited to synonymous and certain intronic variants.
Sources
cspec ↗vcep_f_l_o_w_c_h_a_r_t___f_o_r___a_p_p_l_i_c_a_t_i_o_n___o_f___p_p_3___2_c___b_p_4___2_c___a_n_d___b_p_7
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.05).
0 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
1,142,226 / 1,613,582 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Captured SpliceAI source record
Open source ↗
ClinVar
Captured ClinVar source record
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
Cancer hotspots
Captured Cancer Hotspots source record
Open source ↗
OncoKB
Captured OncoKB source record
Open source ↗
ClinGen CSpec
Captured ClinGen CSpec source record
Open source ↗
All source links
- ClinGen CSpec ↗cspec.genome.network/cspec/ui/svi/doc/135637581
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/12351/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/17-7579472-G-C?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr17-7676154-G-C?dataset=gnomad_r4
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000546.5%3Ac.215C…
- OncoKB ↗www.oncokb.org/gene/TP53/P72R
- COSMIC ↗cancer.sanger.ac.uk/cosmic/login
- Cancer hotspots ↗www.cancerhotspots.org/
Statements for reports
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.707882; MAF= 70.78822%, 1142226/1613582 alleles, homozygotes = 411964) and has highest observed frequency in the European (non-Finnish) population (AF= 0.747582; MAF= 74.75821%, 882123/1179968 alleles, homozygotes = 329809); grpmax FAF= 0.746273.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.662887; MAF= 66.28868%, 186832/281846 alleles, homozygotes = 63926) and has highest observed frequency in the European (non-Finnish) population (AF= 0.73659; MAF= 73.65900%, 94889/128822 alleles, homozygotes = 34940); grpmax FAF= 0.733613.
ClinVar
This variant has been reported in ClinVar as Benign (25 clinical laboratories) and as Uncertain significance (1 clinical laboratory) and as Benign by ClinGen TP53 Variant Curation Expert Panel, ClinGen (expert panel).
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.05).
Functional
OncoKB has not reviewed this specific variant; no variant-level oncogenicity or biological effect is available. Gene-level context: TP53, a tumor suppressor in the DNA damage pathway, is the most frequently mutated gene in cancer.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.