About KRAS
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
KRAS c.24A>G, p.(Val8=)
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 KRAS VCEP v2.3.0. 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: 4
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 4
BA1Stand alone
BA1 · stand alone
This variant is present in gnomAD above the KRAS VCEP BA1 threshold of 0.05% filtering allele frequency. The gnomAD v4.1 grpmax FAF is 0.056632%, which is above the BA1 threshold.
BS1Strong
BS1 · strong
This variant is present in gnomAD above the KRAS VCEP BS1 threshold of 0.025% filtering allele frequency. The observed grpmax FAF is 0.0402% in gnomAD v2.1 and 0.056632% in gnomAD v4.1, both above the BS1 threshold.
BP4Supporting
BP4 · supporting
SpliceAI predicts no significant splice impact for this synonymous variant, with a maximum delta score of 0.02, which supports a negligible effect on splicing and meets BP4 at supporting strength.
BP6Supporting
BP6 · supporting
Expert panel ClinGen RASopathy Variant Curation Expert Panel classified as Likely benign.
Recorded classification: Benign
ClinGen RASopathy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for KRAS Version 2.3.0 v2.3.0 criteria-combination framework: matched Rule17 (1 Benign.Stand Alone) with applied criteria: BS1 strong, BA1 stand-alone benign, BP4 supporting, BP6 supporting benign; 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
742 / 1,612,464 alleles
gnomAD v4.1: 742 / 1,612,464 alleles. Recorded AF 0.000460165. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000253604; MAF= 0.02536%, 71/279964 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000509524; MAF= 0.05095%, 65/127570 alleles, homozygotes = 0); grpmax FAF= 0.000402.
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.
Functional evidence
Statement recorded
OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.
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 KRAS VCEP v2.3.0, with the data and sources behind each one.
28 criteria with recorded statuses: 4 met · 9 not met · 8 not assessed · 7 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
The KRAS c.24A>G (p.Val8=) variant has been reported in ClinVar with an expert panel classification of likely benign, with additional benign and likely benign clinical laboratory submissions.
This variant is present in population databases at a frequency above the KRAS VCEP benign thresholds, with grpmax filtering allele frequencies of 0.0402% in gnomAD v2.1 and 0.056632% in gnomAD v4.1, exceeding the BS1 threshold of 0.025% and the BA1 threshold of 0.05% in v4.1.
SpliceAI predicts no significant splice impact for this variant, with a maximum delta score of 0.02, supporting no expected clinically meaningful effect on splicing.
No criteria match.
Met · 4
BA1 Stand aloneThis variant is present in gnomAD above the KRAS VCEP BA1 threshold of 0.05% filtering allele frequency. The gnomAD v4.1 grpmax FAF is 0.056632%, which is above the BA1 threshold. Details ▾Hide ▴
Rule
KRAS VCEP BA1 Stand Alone: gnomAD filtering allele frequency >=0.05%.
Evidence considered
- gnomAD v4.1 grpmax FAF 0.00056632 (0.056632%)
- KRAS VCEP BA1 threshold >=0.05%
Sources
BS1 StrongThis variant is present in gnomAD above the KRAS VCEP BS1 threshold of 0.025% filtering allele frequency. The observed grpmax FAF is 0.0402% in gnomAD v2.1 and 0.056632% in gnomAD v4.1, both above the BS1 threshold. Details ▾Hide ▴
Rule
KRAS VCEP BS1 Strong: gnomAD filtering allele frequency >=0.025%.
Evidence considered
- gnomAD v2.1 grpmax FAF 0.000402 (0.0402%)
- gnomAD v4.1 grpmax FAF 0.00056632 (0.056632%)
- KRAS VCEP BS1 threshold >=0.025%
Sources
BP4 SupportingSpliceAI predicts no significant splice impact for this synonymous variant, with a maximum delta score of 0.02, which supports a negligible effect on splicing and meets BP4 at supporting strength. Details ▾Hide ▴
Rule
KRAS VCEP BP4 Supporting: for splicing evidence, predicted outcome is negligible or does not match disease mechanism.
Evidence considered
- SpliceAI DS_AG 0.01
- SpliceAI DS_AL 0.02
- SpliceAI DS_DG 0.00
- SpliceAI DS_DL 0.00
- Maximum delta score 0.02
Sources
Not met · 9 · evaluated, threshold not reached
PS1 This variant does not change the amino acid sequence, so it does not meet PS1 for the same amino acid change as a previously established pathogenic variant. Details ▾Hide ▴
Rule
KRAS VCEP PS1 requires the same amino acid change as an established pathogenic variant.
Evidence considered
- Protein consequence p.(Val8=)
Sources
PS3 No approved variant-specific functional study was identified showing a damaging effect for this synonymous KRAS variant, so PS3 is not met. Details ▾Hide ▴
Rule
KRAS VCEP PS3 Supporting requires one approved assay; Moderate requires two or more different approved assays.
Evidence considered
- RASopathy VCEP functional study summary lists KRAS assay references but no variant-specific result for p.(Val8=)
Still missing
- No approved assay result for p.(Val8=) was identified.
Sources
cspec ↗vcep_svi_rasopathy_vcep_v2_approved_functional_studies
PS4 No evidence was identified that this variant is enriched in individuals with a KRAS-related RASopathy, and no exact proband count meeting the KRAS VCEP point thresholds was found, so PS4 is not met. Details ▾Hide ▴
Rule
KRAS VCEP PS4 Supporting requires >=1 point, Moderate >=3 points, Strong >=5 points.
Evidence considered
- ClinVar expert panel classification likely benign
- No exact PS4 point-based case count identified
Still missing
- No affected-case count or case-control enrichment data were identified for this exact variant.
Sources
PM1 Codon 8 is outside the KRAS VCEP PM1 domains P-loop (amino acids 10-17), Switch I (25-40), Switch II (57-64), and SAK (145-156), and no hotspot evidence was identified for this residue, so PM1 is not met. Details ▾Hide ▴
Rule
KRAS VCEP PM1 Moderate applies only to specified functional domains and not to specific amino acid residues.
Evidence considered
- KRAS VCEP PM1 domains begin at amino acid 10
- Variant residue Val8
- Cancer Hotspots: no hotspot row found for KRAS V8
Sources
PM2 This variant is present in gnomAD and therefore does not meet the KRAS VCEP PM2 rule requiring absence from controls. Details ▾Hide ▴
Rule
KRAS VCEP PM2 Supporting requires absence from gnomAD controls.
Evidence considered
- gnomAD v2.1 total AF 0.000253604
- gnomAD v4.1 total AF 0.000460165
Sources
PM4 This variant does not alter protein length and is not an in-frame insertion, in-frame deletion, or stop-loss variant, so PM4 is not met. Details ▾Hide ▴
Rule
KRAS VCEP PM4 applies to protein length changes from in-frame indels or stop-loss variants.
Evidence considered
- Protein consequence p.(Val8=)
Sources
PM5 This variant is synonymous and does not create a novel amino acid substitution, so it does not meet the KRAS VCEP PM5 rule for a different missense change at the same codon. Details ▾Hide ▴
Rule
KRAS VCEP PM5 requires a different pathogenic or likely pathogenic missense residue change at the same codon.
Evidence considered
- Protein consequence p.(Val8=)
- PM5 is specified for missense residue changes
Sources
PP3 Available computational evidence does not support a deleterious effect. SpliceAI predicts no significant splice impact with a maximum delta score of 0.02, and no REVEL, BayesDel, or HCI prior score was available for this synonymous variant. Details ▾Hide ▴
Rule
KRAS VCEP PP3 Supporting requires computational evidence supporting a deleterious effect or splice outcome matching disease mechanism.
Evidence considered
- SpliceAI maximum delta score 0.02
- No REVEL score identified
- No BayesDel score identified
- No HCI prior score identified
Sources
BP1 This variant is a synonymous substitution rather than a truncating loss-of-function variant, so it does not meet the KRAS VCEP BP1 rule. Details ▾Hide ▴
Rule
KRAS VCEP BP1 applies to truncating variants in a gene primarily associated with gain-of-function disease.
Evidence considered
- Protein consequence p.(Val8=)
- PVS1 assessment variant bucket other
Sources
cspec ↗pvs1_variant_assessment
Not assessed · 8 · no assessment recorded
PS2 No confirmed de novo occurrence with maternity and paternity confirmation was identified for this variant, so PS2 could not be assessed. Details ▾Hide ▴
Rule
KRAS VCEP PS2 uses point-based confirmed de novo evidence.
Evidence considered
- No PS2-eligible de novo evidence identified
Still missing
- No confirmed de novo case report was identified.
Sources
PM6 No assumed de novo report without confirmed parentage was identified for this variant, so PM6 could not be assessed. Details ▾Hide ▴
Rule
KRAS VCEP PM6 uses point-based assumed de novo evidence.
Evidence considered
- No PM6-eligible de novo evidence identified
Still missing
- No de novo case report without maternity and paternity confirmation was identified.
Sources
PP1 No segregation data were identified for this variant, so PP1 could not be assessed. Details ▾Hide ▴
Rule
KRAS VCEP PP1 uses informative meioses-based segregation evidence.
Evidence considered
- No segregation evidence identified
Still missing
- No informative meioses or family segregation reports were identified.
Sources
BS2 Population frequency data alone do not establish observation in clinically evaluated unaffected individuals under the KRAS VCEP BS2 point-based framework, so BS2 was not assessed. Details ▾Hide ▴
Rule
KRAS VCEP BS2 uses point-based unaffected-individual evidence rather than population frequency alone.
Evidence considered
- Population observations in gnomAD
- No phenotyped unaffected individual evidence identified
Still missing
- No healthy adult or unaffected family observation data meeting the BS2 point system were identified.
Sources
BS4 No informative non-segregation data were identified for this variant, so BS4 could not be assessed. Details ▾Hide ▴
Rule
KRAS VCEP BS4 Strong requires informative lack of segregation.
Evidence considered
- No BS4 non-segregation evidence identified
Still missing
- No family data showing lack of segregation were identified.
Sources
BP2 No phase data or evidence of another pathogenic RASopathy variant in the same gene were identified, so BP2 could not be assessed. Details ▾Hide ▴
Rule
KRAS VCEP BP2 uses point-based evidence for a second molecular explanation in the same gene.
Evidence considered
- No phase or second-variant evidence identified
Still missing
- No phase information or second molecular diagnosis in KRAS was identified.
Sources
BP5 No evidence was identified for an alternative molecular explanation of a RASopathy phenotype in another gene, so BP5 could not be evaluated. Details ▾Hide ▴
Rule
KRAS VCEP BP5 uses point-based evidence for an alternative molecular explanation.
Evidence considered
- No alternate molecular diagnosis evidence identified
Still missing
- No phenotype-specific alternate molecular diagnosis data were identified.
Sources
BP7 This synonymous variant has no predicted splice effect by SpliceAI (max delta score 0.02), but the KRAS VCEP rule for BP7 also requires that the altered nucleotide is not highly conserved, and no conservation evidence was identified here. Details ▾Hide ▴
Rule
KRAS VCEP BP7 Supporting: synonymous variant with no predicted splice impact and nucleotide not highly conserved.
Evidence considered
- Synonymous change p.(Val8=)
- SpliceAI max delta score 0.02
- KRAS VCEP BP7 requires no splice impact and lack of high conservation
Still missing
- No nucleotide conservation evidence was identified to complete the KRAS VCEP BP7 rule.
Sources
Not applicable · 7· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/APVS1 is not applicable in the KRAS VCEP framework for this variant, and this synonymous change is not a null variant within the generic PVS1 categories. Details ▾Hide ▴
Rule
KRAS VCEP PVS1 not applicable for this framework/variant context.
Evidence considered
- KRAS VCEP marks PVS1 not applicable
- Variant is synonymous p.(Val8=)
- Generic PVS1 scaffold: variant does not fall into null-variant buckets
Sources
PM3 N/APM3 is not applicable in the KRAS RASopathy VCEP framework. Details ▾Hide ▴
Rule
KRAS VCEP PM3 not applicable.
Evidence considered
- KRAS VCEP marks PM3 not applicable
Sources
PP2 N/APP2 is not applicable in this VCEP framework. Details ▾Hide ▴
Rule
KRAS VCEP PP2 not applicable.
Evidence considered
- KRAS VCEP marks PP2 not applicable
Sources
PP4 N/APP4 is not applicable in this VCEP framework because phenotype-based evidence is handled through other RASopathy-specific criteria. Details ▾Hide ▴
Rule
KRAS VCEP PP4 not applicable.
Evidence considered
- KRAS VCEP marks PP4 not applicable
Sources
PP5 N/APP5 is not for use in this VCEP framework. Details ▾Hide ▴
Rule
KRAS VCEP PP5 not applicable.
Evidence considered
- KRAS VCEP marks PP5 not applicable
Sources
BS3 N/ABS3 is not applicable in the KRAS RASopathy VCEP framework. Details ▾Hide ▴
Rule
KRAS VCEP BS3 not applicable.
Evidence considered
- KRAS VCEP marks BS3 not applicable
Sources
BP3 N/ABP3 is not applicable in the KRAS RASopathy VCEP framework. Details ▾Hide ▴
Rule
KRAS VCEP BP3 not applicable.
Evidence considered
- KRAS VCEP marks BP3 not applicable
Sources
Identifiers
- Gene
- KRAS
- Transcript
- NM_004985.4
- Coding (HGVS c.)
- NM_004985.4:c.24A>G
- Protein (HGVS p.)
- NP_004976.2:p.(Val8=)
- GRCh38
- chr12:25245361 T>C
- GRCh37
- chr12:25398295 T>C
Gene diagram
Every interpreted variant in KRAS, mapped onto the exon structure of NM_004985.4. Select a row to find it on the plot.
KRASNM_004985.4
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 KRAS
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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
742 / 1,612,464 alleles
AF 0.00046 · 0 homozygotes · FAF 0.000566
gnomAD v2.1
71 / 279,964 alleles
AF 0.000254 · 0 homozygotes · FAF 0.000402
By genetic ancestry
gnomAD v4.1
AF 0.00046 · 742 / 1,612,464 alleles · 0 hom · FAF 0.00057
| European (non-Finnish)712 / 1,179,132 | 0.0006 |
| Remaining individuals23 / 62,406 | 0.00037 |
| African/African American5 / 74,930 | 6.7e-05 |
| Admixed American1 / 59,894 | 1.7e-05 |
| European (Finnish)1 / 63,990 | 1.6e-05 |
0 alternate alleles recorded in 5 other groups: Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish.
gnomAD v2.1
AF 0.00025 · 71 / 279,964 alleles · 0 hom · FAF 0.0004
| European (non-Finnish)65 / 127,570 | 0.00051 |
| Remaining individuals3 / 7,176 | 0.00042 |
| African/African American2 / 24,702 | 8.1e-05 |
| European (Finnish)1 / 25,044 | 4e-05 |
0 alternate alleles recorded in 4 other groups: Admixed American, Ashkenazi Jewish, East Asian, South Asian.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.000460165; MAF= 0.04602%, 742/1612464 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000603834; MAF= 0.06038%, 712/1179132 alleles, homozygotes = 0); grpmax FAF= 0.00056632.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000253604; MAF= 0.02536%, 71/279964 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000509524; MAF= 0.05095%, 65/127570 alleles, homozygotes = 0); grpmax FAF= 0.000402.
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
BP4 SupportingSpliceAI predicts no significant splice impact for this synonymous variant, with a maximum delta score of 0.02, which supports a negligible effect on splicing and meets BP4 at supporting strength. Details ▾Hide ▴
Rule
KRAS VCEP BP4 Supporting: for splicing evidence, predicted outcome is negligible or does not match disease mechanism.
Evidence considered
- SpliceAI DS_AG 0.01
- SpliceAI DS_AL 0.02
- SpliceAI DS_DG 0.00
- SpliceAI DS_DL 0.00
- Maximum delta score 0.02
Sources
PP3 Available computational evidence does not support a deleterious effect. SpliceAI predicts no significant splice impact with a maximum delta score of 0.02, and no REVEL, BayesDel, or HCI prior score was available for this synonymous variant. Details ▾Hide ▴
Rule
KRAS VCEP PP3 Supporting requires computational evidence supporting a deleterious effect or splice outcome matching disease mechanism.
Evidence considered
- SpliceAI maximum delta score 0.02
- No REVEL score identified
- No BayesDel score identified
- No HCI prior score identified
Sources
BP7 This synonymous variant has no predicted splice effect by SpliceAI (max delta score 0.02), but the KRAS VCEP rule for BP7 also requires that the altered nucleotide is not highly conserved, and no conservation evidence was identified here. Details ▾Hide ▴
Rule
KRAS VCEP BP7 Supporting: synonymous variant with no predicted splice impact and nucleotide not highly conserved.
Evidence considered
- Synonymous change p.(Val8=)
- SpliceAI max delta score 0.02
- KRAS VCEP BP7 requires no splice impact and lack of high conservation
Still missing
- No nucleotide conservation evidence was identified to complete the KRAS VCEP BP7 rule.
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.02).
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
742 / 1,612,464 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/643243114
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/45119/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/12-25398295-T-C?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr12-25245361-T-C?dataset=gn…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_004985.4%3Ac.24A%…
- OncoKB ↗www.oncokb.org/gene/KRAS/V8=
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=108083335
- 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= 0.000460165; MAF= 0.04602%, 742/1612464 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000603834; MAF= 0.06038%, 712/1179132 alleles, homozygotes = 0); grpmax FAF= 0.00056632.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000253604; MAF= 0.02536%, 71/279964 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000509524; MAF= 0.05095%, 65/127570 alleles, homozygotes = 0); grpmax FAF= 0.000402.
ClinVar
This variant has been reported in ClinVar as Likely benign (11 clinical laboratories) and as Benign (3 clinical laboratories) and as Likely benign by ClinGen RASopathy Variant Curation Expert Panel (expert panel).
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.02).
Functional
OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV99778613, n = 1 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.