Back
LYFE SCIENCES
Project: HERA
NM_002524.4:c.112-8A>G
p.?  ·  NRAS
Starting
Initialising…
0%
Legacy Engine
Ready
View Legacy →
Classification rationale
1

The NRAS c.112-8A>G (p.?) variant has been reported in ClinVar, where the aggregate classification is likely benign and expert panel review is present.

clinvar ↗
2

This variant is present in population databases, with gnomAD v2.1 total AF 0.02558% and grpmax FAF 0.03711%, and gnomAD v4.1 total AF 0.03946% and grpmax FAF 0.04727%, which is above the NRAS RASopathy BS1 threshold of 0.025% but below the BA1 threshold of 0.05%.

gnomad_v2 ↗ gnomad_v4 ↗ cspec ↗
3

SpliceAI predicts no significant splice effect for this variant, with a maximum delta score of 0.02, which does not support a deleterious splicing prediction.

spliceai ↗ cspec ↗
Applied criteria
Met
Not met
Not assessed
N/A
Very strong
Strong
Moderate
Supporting
Pathogenic evidence
PVS
PVS1
PS
PS1
PS2
PS3
PS4
PM
PM1
PM2
PM3
PM4
PM5
PM6
PP
PP1
PP2
PP3
PP4
PP5
Benign evidence
BA
BA1
BS
BS1
BS2
BS3
BS4
BP
BP1
BP2
BP3
BP4
BP5
BP6
BP7
PVS1
—
—
Rationale
Select a criterion to inspect its explanation.
Evidence used
  • —
Gaps remaining
  • —
Rule
—
Publications
—
Research and evidence
gnomAD v2.1 evidence
v2.1
gnomAD v4.1 evidence
v4.1
01
Population
gnomAD v2.1This variant is present in gnomAD v2.1 (AF= 0.000255817; MAF= 0.02558%, 71/277542 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000487061; MAF= 0.04871%, 62/127294 alleles, homozygotes = 0); grpmax FAF= 0.00037107.
gnomAD v4.1This variant is present in gnomAD v4.1 (AF= 0.000394632; MAF= 0.03946%, 529/1340490 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000510694; MAF= 0.05107%, 499/977102 alleles, homozygotes = 0); grpmax FAF= 0.00047274.
gnomAD v2 ↗ gnomAD v4 ↗
ClinVar evidence
02
ClinVar
This variant has been reported in ClinVar as Likely benign (4 clinical laboratories) and as Benign (2 clinical laboratories) and as Likely Benign (1 clinical laboratory) and as Uncertain significance (1 clinical laboratory) and as Likely Benign by ClinGen RASopathy Variant Curation Expert Panel (expert panel).
ClinVar ↗
03
Functional
No functional summary recorded.
OncoKB ↗
In silico evidence
04
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.02).
SpliceAI ↗
COSMIC evidence
05
COSMIC
This variant has not previously been reported in somatic cancers (COSMIC).
COSMIC ↗
06
Cancer hotspots
No cancer hotspot summary recorded.