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CREB3L3
Final classification
Benign
CREB3L3 c.313G>A · p.Gly105Arg
CREB3L3

The CREB3L3 c.313G>A (p.Gly105Arg, p.G105R) variant has been reported in ClinVar as Benign with criteria provided by a single submitter representing 2 clinical laboratory submissions.

Gene
CREB3L3
Transcript
NM_032607.3
HGVS · transcript:coding
NM_032607.3:c.313G>A
Consequence
N/A
GRCh38
chr19:4157151 G>A
GRCh37
chr19:4157148 G>A
Basis gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: BA1 stand-alone benign, BS1 strong benign, BP4 supporting benign; combination = 1 stand-alone benign, which maps to Benign. ▾
gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: BA1 stand-alone benign, BS1 strong benign, BP4 supporting benign; combination = 1 stand-alone benign, which maps to Benign.
Classification rationale
BA1BS1BP4 Benign
CREB3L3 c.313G>A

The CREB3L3 c.313G>A (p.Gly105Arg, p.G105R) variant has been reported in ClinVar as Benign with criteria provided by a single submitter representing 2 clinical laboratory submissions.1 This variant is common in population databases, with gnomAD v2.1 showing a total allele frequency of 0.37177% and an East Asian allele frequency of 3.44274%, and gnomAD v4.1 showing a total allele frequency of 0.21551% and an East Asian allele frequency of 3.43413%, which is above the default benign population thresholds.2 Computational evidence does not support a damaging effect, with SpliceAI predicting no significant splice impact (maximum delta score 0.02), REVEL 0.257, and BayesDel -0.423809.3

BA1 + BS1 + BP4 → Benign
1 clinvar ↗
2 gnomad_v2 ↗gnomad_v4 ↗
3 spliceai ↗revelbayesdel
Gene diagram · NM_032607.3 · variants mapped to exon structure
CREB3L3 NM_032607.3
Fetching transcript structure from UCSC…
Applied criteria · 3 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 screenshot
      gnomAD v4.1
      gnomAD v2.1 screenshot
      gnomAD v2.1
      v4.1
      This variant is present in gnomAD v4.1 (AF= 0.00215512; MAF= 0.21551%, 3478/1613834 alleles, homozygotes = 37) and has highest observed frequency in the East Asian population (AF= 0.0343413; MAF= 3.43413%, 1540/44844 alleles, homozygotes = 31); grpmax FAF= 0.0329142.
      v2.1
      This variant is present in gnomAD v2.1 (AF= 0.0037177; MAF= 0.37177%, 1047/281626 alleles, homozygotes = 14) and has highest observed frequency in the East Asian population (AF= 0.0344274; MAF= 3.44274%, 686/19926 alleles, homozygotes = 13); grpmax FAF= 0.0321736.
      Allele frequency by ancestry
      three datasets · side by side
      gnomAD v4.1
      0.22% · 3478 / 1,613,834
      37 hom · FAF 3.3%
      East Asian
      1540 / 44,844
      3.4%
      31 hom
      Remaining individuals
      199 / 62,498
      0.32%
      2 hom
      Admixed American
      164 / 59,962
      0.27%
      3 hom
      European (non-Finnish)
      1389 / 1,179,984
      0.12%
      1 hom
      Middle Eastern
      7 / 6,060
      0.12%
      African/African American
      68 / 74,942
      0.091%
      European (Finnish)
      49 / 63,966
      0.077%
      South Asian
      61 / 91,062
      0.067%
      Ashkenazi Jewish
      1 / 29,606
      0.0034%
      + 1 not observed (Amish)
      gnomAD v2.1
      0.37% · 1047 / 281,626
      14 hom · FAF 3.2%
      East Asian
      686 / 19,926
      3.4%
      13 hom
      Remaining individuals
      25 / 7,212
      0.35%
      Admixed American
      117 / 35,432
      0.33%
      1 hom
      European (non-Finnish)
      170 / 128,048
      0.13%
      European (Finnish)
      17 / 25,110
      0.068%
      African/African American
      15 / 24,938
      0.06%
      South Asian
      17 / 30,606
      0.056%
      + 1 not observed (Ashkenazi Jewish)
      gnomAD v4 ↗ gnomAD v2 ↗
      ClinVar screenshot
      ClinVar
      This variant has been reported in ClinVar as Benign (2 clinical laboratories).
      ClinVar ↗
      SpliceAI screenshot
      In silico
      SpliceAI predicts no significant splice impact for this variant (max delta score = 0.02). REVEL score = 0.257. BayesDel score = -0.423809.
      SpliceAI ↗
      Functional No data
      No calibrated functional assay or RNA evidence was identified for this variant.
      OncoKB ↗
      COSMIC screenshot
      COSMIC
      Somatic evidence Not in COSMIC / hotspots
      COSMIC
      This variant has not previously been reported in somatic cancers (COSMIC).
      Hotspots
      This variant does not lie in a statistically significant cancer hotspot.
      COSMIC ↗ Hotspots ↗
      Sources & reference links
      7Sources
      ClinVar
      gnomAD v2.1
      gnomAD v4.1
      SpliceAI
      OncoKB
      COSMIC
      Cancer hotspots