Classification rationale

BS1BA1BP4BP6 Benign

KRAS c.24A>G

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.¹ 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 v4.1.² 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.³

BS1 + BA1 + BP4 + BP6 → Benign

1 clinvar ↗

2 cspec ↗gnomad_v2 ↗gnomad_v4 ↗

3 spliceai ↗

Gene diagram · NM_004985.4 · variants mapped to exon structure

KRAS NM_004985.4

Fetching transcript structure from UCSC…

Applied criteria · 4 met · select any tile

Met

Not met

Not assessed

N/A

Strength very strong supporting

Pathogenic evidence

PVS

PS

PM

PP

Benign evidence

BA

BS

BP

—

Rationale

Select a criterion.

Sources

Evidence used

Gaps remaining

Rule

—

Research & evidence

Population frequency · supports benign

gnomAD v4.1

gnomAD v2.1

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.

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.

Allele frequency by ancestry

three datasets · side by side

gnomAD v4.1

0.046% · 742 / 1,612,464
0 hom · FAF 0.057%

European (non-Finnish) 712 / 1,179,132	0.06%
Remaining individuals 23 / 62,406	0.037%
African/African American 5 / 74,930	0.0067%
Admixed American 1 / 59,894	0.0017%
European (Finnish) 1 / 63,990	0.0016%

+ 5 not observed (Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish)

gnomAD v2.1

0.025% · 71 / 279,964
0 hom · FAF 0.04%

European (non-Finnish) 65 / 127,570	0.051%
Remaining individuals 3 / 7,176	0.042%
African/African American 2 / 24,702	0.0081%
European (Finnish) 1 / 25,044	0.004%

+ 4 not observed (Admixed American, Ashkenazi Jewish, East Asian, South Asian)

gnomAD v4 ↗ gnomAD v2 ↗

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).

ClinVar ↗

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.02).

SpliceAI ↗

Functional Unknown Oncogenic Effect

OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.

OncoKB ↗

COSMIC

Cancer hotspots

Somatic evidence Not in COSMIC / hotspots

COSMIC

This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV99778613, n = 1 times).

Hotspots

This variant does not lie in a statistically significant hotspot.

COSMIC ↗ Hotspots ↗

Sources & reference links

8Sources

CSpec VCEP

ClinVar

gnomAD v2.1

gnomAD v4.1

SpliceAI

OncoKB

COSMIC

Cancer hotspots