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ETV6c.329-15C>ALikely benign
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Variant interpretation report

ETV6 c.329-15C>A, p.?

NM_001987.4:c.329-15C>A NP_001978.1:p.? View identifiers
Classification
Likely benign

Variant description:

No variant summary was recorded for this case.

Five-step scale from benign to pathogenic. This variant is likely benign. Select a step to read what it means.

Likely benign.A likely benign classification under the recorded framework.

In plain language

Gene-level background from the recorded interpretation.

About ETV6

No gene-level summary was recorded for this case.

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 Not recorded. 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: 1 Benign evidence criteria: 2
Pathogenic criteria applied · 1
PM2Supporting
PM2 · supporting

NM_001987.4:c.329-15C>A is present in gnomAD at extremely low frequency: AF=0.00495% (14/282,700 alleles) in v2.1 and AF=0.00564% (91/1,613,872 alleles) in v4.1, with no homozygotes observed. The allele frequency is well below the 0.1% threshold for PM2.

Benign criteria applied · 2
BP4Supporting
BP4 · supporting

Multiple lines of in silico evidence predict no impact. SpliceAI predicts no significant splicing alteration (max delta score 0.01, well below the 0.02 threshold). REVEL and BayesDel are not applicable to this intronic variant. The SpliceAI result supports a benign interpretation.

BP6Supporting
BP6 · supporting

ClinVar reports this variant as Likely benign by a clinical testing laboratory (Labcorp Genetics, formerly Invitae) with criteria provided (ClinVarID 1908625, SCV002946987). This constitutes a reputable source supporting a benign classification.

Recorded classification: Likely 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: PM2 supporting, BP4 supporting benign, BP6 supporting benign; combination = 1 supporting + 2 supporting benign, which maps to Likely 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
91 / 1,613,872 alleles

gnomAD v4.1: 91 / 1,613,872 alleles. Recorded AF 5.63861e-05. Recorded homozygote count 0.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 4.95225e-05; MAF= 0.00495%, 14/282700 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000100658; MAF= 0.01007%, 13/129150 alleles, homozygotes = 0); grpmax FAF= 5.378e-05.

gnomAD-Canada

Not available in gnomAD-Canada v1.0.

Applied · PM2 →
gnomAD v4.1 ↗gnomAD v2.1 ↗gnomAD-Canada ↗
SpliceAI score
0.010 maximum delta

Recorded SpliceAI maximum delta score: 0.010. Refer to the recorded PP3/BP4 rationale for interpretation.

Applied · BP4 → SpliceAI ↗
No screenshot for this evidence
Functional evidence
Not recorded

No standalone functional evidence summary is recorded in evidence_summary.functional.

No listed criterion applied OncoKB ↗
Somatic evidence
No matching record reported

This variant has not previously been reported in somatic cancers (COSMIC).

Context only COSMIC ↗
For specialists

Technical detail

ACMG/AMP criteria under Not recorded, with the data and sources behind each one.

27 criteria with recorded statuses: 3 met · 3 not met · 11 not assessed · 10 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic
PVS1PS1PS2PS3PS4PM1PM2PM5PM6PP1PP2PP3PP4PP5PS5
Benign
BA1BS1BS2BS3BS4BP1BP2BP3BP4BP5BP6BP7
Met Not met Not assessed Not applicable

NM_001987.4:c.329-15C>A is an intronic substitution in ETV6 (intron 3, c.329-15) with no predicted splicing impact (SpliceAI max delta 0.01).

This variant is present in gnomAD at very low frequency (v2.1: 14/282,700 alleles, AF=0.00495%; v4.1: 91/1,613,872 alleles, AF=0.00564%) with no homozygotes observed.

ClinVar reports this variant as Likely benign by Labcorp Genetics/Invitae (ClinVarID 1908625, SCV002946987), with criteria provided.

In silico evidence supports a benign interpretation: SpliceAI predicts no splicing alteration, and no computational tool suggests a deleterious effect.

Met · 3

PM2 SupportingNM_001987.4:c.329-15C>A is present in gnomAD at extremely low frequency: AF=0.00495% (14/282,700 alleles) in v2.1 and AF=0.00564% (91/1,613,872 alleles) in v4.1, with no homozygotes observed. The allele frequency is well below the 0.1% threshold for PM2. Details ▾Hide ▴
Evidence considered
  • gnomAD v2.1: 14/282
  • 700 alleles
  • AF=4.95e-05 (0.00495%)
  • 0 homozygotes
  • grpmax FAF=5.38e-05
  • gnomAD v4.1: 91/1
  • 613
  • 872 alleles
  • AF=5.64e-05 (0.00564%)
  • grpmax FAF=6.15e-05
  • Highest subpopulation: European (non-Finnish) at AF=0.00746% (v4.1)
Sources
gnomad_v2 ↗gnomad_v4 ↗
BP4 SupportingMultiple lines of in silico evidence predict no impact. SpliceAI predicts no significant splicing alteration (max delta score 0.01, well below the 0.02 threshold). REVEL and BayesDel are not applicable to this intronic variant. The SpliceAI result supports a benign interpretation. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta score: 0.01 (acceptor gain
  • acceptor loss
  • donor gain
  • donor loss all at or near zero)
  • No in silico predictors suggest a deleterious effect
Sources
spliceai ↗
BP6 SupportingClinVar reports this variant as Likely benign by a clinical testing laboratory (Labcorp Genetics, formerly Invitae) with criteria provided (ClinVarID 1908625, SCV002946987). This constitutes a reputable source supporting a benign classification. Details ▾Hide ▴
Evidence considered
  • ClinVar classification: Likely benign
  • criteria provided
  • single submitter (Labcorp/Invitae)
Sources
clinvar ↗

Not met · 3 · evaluated, threshold not reached

PP3 Multiple lines of in silico evidence do not support a deleterious effect. SpliceAI predicts no significant splice impact (max delta score 0.01). REVEL and BayesDel are not applicable to this intronic variant. HCI prior is not available for ETV6. No computational evidence supports pathogenicity. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta score: 0.01 (acceptor gain
  • acceptor loss
  • donor gain
  • donor loss all near zero)
  • REVEL: not available (intronic variant)
  • BayesDel: not available (intronic variant)
  • HCI prior: gene not supported
Sources
spliceai ↗
BA1 NM_001987.4:c.329-15C>A has an allele frequency of ~0.005% in gnomAD, well below the 1% threshold required for BA1 (stand-alone benign). Details ▾Hide ▴
Evidence considered
  • gnomAD v2.1 total AF: 0.00495%
  • gnomAD v4.1 total AF: 0.00564%
  • Highest subpopulation AF (NFE
  • v4.1): 0.00746%
Sources
gnomad_v2 ↗gnomad_v4 ↗
BS1 NM_001987.4:c.329-15C>A has an allele frequency of ~0.005% in gnomAD, well below the 0.3% threshold for BS1 (strong benign population frequency). Details ▾Hide ▴
Evidence considered
  • gnomAD v2.1 total AF: 0.00495%
  • gnomAD v4.1 total AF: 0.00564%
  • Highest subpopulation AF (NFE
  • v4.1): 0.00746%
Sources
gnomad_v2 ↗gnomad_v4 ↗

Not assessed · 11 · no assessment recorded

PS2 No de novo observation data for NM_001987.4:c.329-15C>A identified in ClinVar, literature, or any evidence source. Details ▾Hide ▴
Still missing
  • No de novo data available for this variant.
PS3 No well-established functional studies evaluating the biological effect of NM_001987.4:c.329-15C>A were identified. SpliceAI (max delta 0.01) is an in silico predictor, not a functional assay, and is considered under BP4. Details ▾Hide ▴
Still missing
  • No in vitro or in vivo functional studies for this variant.
PS4 No case-control or cohort studies reporting NM_001987.4:c.329-15C>A prevalence in affected individuals were identified. The sole associated publication (PMID:28492532) is a methodology paper describing the Sherloc classification framework and does not report variant-specific patient observations. Details ▾Hide ▴
Still missing
  • No case-control or prevalence data for this variant in disease cohorts.
PM6 No de novo observation with unconfirmed or confirmed parentage identified for NM_001987.4:c.329-15C>A in ClinVar or literature. Details ▾Hide ▴
Still missing
  • No de novo data available.
PP1 No co-segregation data available for NM_001987.4:c.329-15C>A. No family studies or pedigrees were identified in ClinVar or literature. Details ▾Hide ▴
Still missing
  • No co-segregation or family study data.
PP4 No phenotype specificity data available for NM_001987.4:c.329-15C>A. No patient phenotype descriptions specific to this variant were found in ClinVar submissions or literature. Details ▾Hide ▴
Still missing
  • No variant-specific phenotype data available.
BS2 No data on trans or cis configurations with pathogenic variants available for NM_001987.4:c.329-15C>A. While the variant is observed in gnomAD (a predominantly healthy population cohort), the traditional BS2 criterion requires observation in trans with a dominant pathogenic variant or in cis with a pathogenic variant. Details ▾Hide ▴
Still missing
  • No trans/cis phase data with pathogenic variants.
BS3 No well-established functional studies demonstrating no deleterious effect of NM_001987.4:c.329-15C>A were identified. SpliceAI prediction is an in silico tool addressed under BP4. Details ▾Hide ▴
Still missing
  • No in vitro or in vivo functional studies demonstrating a benign effect.
BS4 No segregation data available to evaluate lack of segregation with disease for NM_001987.4:c.329-15C>A. Details ▾Hide ▴
Still missing
  • No family segregation data.
BP2 No data on observation in trans with a dominant pathogenic variant or in cis with a pathogenic variant for NM_001987.4:c.329-15C>A. Details ▾Hide ▴
Still missing
  • No trans/cis phase data available.
BP5 No alternative molecular cause was identified to explain the phenotype. BP5 requires observation of a molecular basis for disease in a case where the variant in question is also present. Details ▾Hide ▴
Still missing
  • No data on alternative molecular causes in this case.
Not applicable · 10· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/AIntronic variant at c.329-15 position in ETV6 intron 3; not a null variant (nonsense, frameshift, canonical ±1,2 splice). PVS1 is not applicable to non-null intronic variants under the generic PVS1 framework (PMC6185798). Details ▾Hide ▴
Evidence considered
  • Variant class is intronic (c.329-15C>A)
  • PVS1 variant bucket is 'other' and generic PVS1 framework does not apply.
Sources
pvs1_generic_framework ↗pvs1_variant_assessment
PS1 N/AIntronic variant; not a missense change at an amino acid residue with a known pathogenic missense variant. PS1 requires same amino acid change as an established pathogenic variant. Details ▾Hide ▴
Evidence considered
  • Variant is intronic (c.329-15C>A)
  • no amino acid change.
PM1 N/ANo mutational hotspot or functional domain enrichment data for NM_001987.4:c.329-15C>A. The variant lies in intron 3, not in a well-characterized functional domain with established pathogenic missense enrichment. Details ▾Hide ▴
Evidence considered
  • Hotspot analysis: residue_significant=false
  • exact variant not listed.
PM5 N/AIntronic variant at c.329-15; no amino acid change. PM5 requires a different missense change at the same residue as a known pathogenic missense variant and does not apply to intronic substitutions. Details ▾Hide ▴
Evidence considered
  • Variant is intronic
  • no residue-level comparison possible.
PP2 N/AIntronic variant; not a missense change. PP2 applies only to missense variants in genes with a low rate of benign missense variation. Details ▾Hide ▴
Evidence considered
  • Variant is intronic (c.329-15C>A).
PP5 N/AClinVar reports this variant as Likely benign (single submitter, Labcorp/Invitae). PP5 requires a reputable source asserting pathogenicity; a benign classification does not satisfy PP5. Details ▾Hide ▴
Evidence considered
  • ClinVar classification: Likely benign (ClinVarID 1908625).
Sources
clinvar ↗
BP1 N/AIntronic variant; not a missense change. BP1 applies to missense variants in genes where a truncating mechanism is the primary cause of disease. Details ▾Hide ▴
Evidence considered
  • Variant is intronic (c.329-15C>A).
BP3 N/AThis is a substitution, not an in-frame indel in a non-repeat region. BP3 does not apply. Details ▾Hide ▴

No further detail was recorded.

BP7 N/ANM_001987.4:c.329-15C>A is an intronic variant, not a synonymous (silent) variant. BP7 applies to synonymous variants with no predicted splice impact. Details ▾Hide ▴
Evidence considered
  • Variant is intronic
  • not synonymous.
PS5 N/AClinVar reports this variant as Likely benign (single submitter, Labcorp/Invitae). PS5 requires a reputable source asserting pathogenicity; a benign classification does not satisfy PS5. Details ▾Hide ▴
Evidence considered
  • ClinVar classification: Likely benign (ClinVarID 1908625).
Sources
clinvar ↗

Identifiers

Gene
ETV6
Transcript
NM_001987.4
Coding (HGVS c.)
NM_001987.4:c.329-15C>A
Protein (HGVS p.)
NP_001978.1:p.?
GRCh38
chr12:11853412 C>A
GRCh37
chr12:12006346 C>A
ClinVar
1908625

Gene diagram

Every interpreted variant in ETV6, mapped onto the exon structure of NM_001987.4. Select a row to find it on the plot.

ETV6NM_001987.4
Fetching transcript structure from UCSC…
gnomAD v4.1 91 / 1,613,872 alleles AF 5.64e-05 · 0 homozygotes · FAF 6.15e-05
gnomAD v2.1 14 / 282,700 alleles AF 4.95e-05 · 0 homozygotes · FAF 5.38e-05
gnomAD-Canada v1.0 Allele count data not recorded

By genetic ancestry

gnomAD v4.1

AF 5.6e-05 · 91 / 1,613,872 alleles · 0 hom · FAF 6.1e-05
European (non-Finnish)88 / 1,179,940 7.5e-05
Remaining individuals2 / 62,474 3.2e-05
African/African American1 / 74,900 1.3e-05
0 alternate alleles recorded in 7 other groups: Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish.

gnomAD v2.1

AF 5e-05 · 14 / 282,700 alleles · 0 hom · FAF 5.4e-05
European (non-Finnish)13 / 129,150 0.0001
African/African American1 / 24,956 4e-05
0 alternate alleles recorded in 6 other groups: Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), Remaining individuals, South Asian.

Statements

gnomAD v4.1

This variant is present in gnomAD v4.1 (AF= 5.63861e-05; MAF= 0.00564%, 91/1613872 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 7.45801e-05; MAF= 0.00746%, 88/1179940 alleles, homozygotes = 0); grpmax FAF= 6.146e-05.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 4.95225e-05; MAF= 0.00495%, 14/282700 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000100658; MAF= 0.01007%, 13/129150 alleles, homozygotes = 0); grpmax FAF= 5.378e-05.

gnomAD-Canada

Not available in gnomAD-Canada v1.0.

SpliceAI and Pangolin

SpliceAI acceptor lossat +15 bp
0.000
SpliceAI acceptor gainat +41 bp
0.000
SpliceAI donor lossat +237 bp
0.010
SpliceAI donor gainat +14 bp
0.000
Pangolin splice lossmagnitude shown
-0.000
Pangolin splice gain
0.000

Other predictors

REVEL
Not available
BayesDel
Not available

How the predictions were used

BP4 SupportingMultiple lines of in silico evidence predict no impact. SpliceAI predicts no significant splicing alteration (max delta score 0.01, well below the 0.02 threshold). REVEL and BayesDel are not applicable to this intronic variant. The SpliceAI result supports a benign interpretation. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta score: 0.01 (acceptor gain
  • acceptor loss
  • donor gain
  • donor loss all at or near zero)
  • No in silico predictors suggest a deleterious effect
Sources
spliceai ↗
PP3 Multiple lines of in silico evidence do not support a deleterious effect. SpliceAI predicts no significant splice impact (max delta score 0.01). REVEL and BayesDel are not applicable to this intronic variant. HCI prior is not available for ETV6. No computational evidence supports pathogenicity. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta score: 0.01 (acceptor gain
  • acceptor loss
  • donor gain
  • donor loss all near zero)
  • REVEL: not available (intronic variant)
  • BayesDel: not available (intronic variant)
  • HCI prior: gene not supported
Sources
spliceai ↗
BP7 N/ANM_001987.4:c.329-15C>A is an intronic variant, not a synonymous (silent) variant. BP7 applies to synonymous variants with no predicted splice impact. Details ▾Hide ▴
Evidence considered
  • Variant is intronic
  • not synonymous.

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01).

1 paper record listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.

Recorded publications

  • Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.
    Nykamp K et al. · 2017
    Describes the Sherloc framework, a comprehensive refinement of the ACMG-AMP variant classification criteria. This is a methodology paper that does not report or discuss the specific variant NM_001987.4:c.329-15C>A in ETV6.
    Does not name this variant
    PMID 28492532 ↗

Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.

gnomAD v4.1 91 / 1,613,872 recorded alleles Open source ↗
gnomAD v2.1 Captured gnomAD v2.1 source record Open source ↗
SpliceAI Lookup Recorded maximum delta 0.010 Open source ↗
ClinVar 1 Likely benign Open source ↗
COSMIC Captured COSMIC source record Open source ↗

All source links

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= 5.63861e-05; MAF= 0.00564%, 91/1613872 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 7.45801e-05; MAF= 0.00746%, 88/1179940 alleles, homozygotes = 0); grpmax FAF= 6.146e-05.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 4.95225e-05; MAF= 0.00495%, 14/282700 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000100658; MAF= 0.01007%, 13/129150 alleles, homozygotes = 0); grpmax FAF= 5.378e-05.

gnomAD-Canada

Not available in gnomAD-Canada v1.0.

ClinVar

This variant has been reported in ClinVar as Likely benign (1 clinical laboratory). (ClinVarID = 1908625)

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01).

Somatic

This variant has not previously been reported in somatic cancers (COSMIC).