Classification rationale

PM2 BP4BP6 Likely Benign

ETV6 c.329-15C>A

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).¹ 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.² ClinVar reports this variant as Likely benign by Labcorp Genetics/Invitae (ClinVarID 1908625, SCV002946987), with criteria provided.³ In silico evidence supports a benign interpretation: SpliceAI predicts no splicing alteration, and no computational tool suggests a deleterious effect.⁴

PM2 + BP4 + BP6 → Likely Benign

1 spliceai ↗

2 gnomad_v2 ↗gnomad_v4 ↗

3 clinvar ↗

4 spliceai ↗

Gene diagram · NM_001987.4 · variants mapped to exon structure

ETV6 NM_001987.4

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

gnomAD v2.1

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.

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.

🇨🇦 CA

Not available in gnomAD-Canada v1.0.

Allele frequency by ancestry

three datasets · side by side

gnomAD v4.1

0.0056% · 91 / 1,613,872
0 hom · FAF 0.0061%

European (non-Finnish) 88 / 1,179,940	0.0075%
Remaining individuals 2 / 62,474	0.0032%
African/African American 1 / 74,900	0.0013%

+ 7 not observed (Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish)

gnomAD v2.1

0.005% · 14 / 282,700
0 hom · FAF 0.0054%

European (non-Finnish) 13 / 129,150	0.01%
African/African American 1 / 24,956	0.004%

+ 6 not observed (Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), Remaining individuals, South Asian)

gnomAD Canada 🇨🇦

Absent · 0 / ?
0 hom

Not observed in any ancestry group.

gnomAD v4 ↗ gnomAD v2 ↗ gnomAD 🇨🇦 ↗

ClinVar

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

ClinVar ↗

In silico

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

SpliceAI ↗

Functional No data

No calibrated functional assay or RNA evidence was identified for this variant.

OncoKB ↗

COSMIC

Somatic evidence

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 ↗

Sources & reference links

7Sources

ClinVar

gnomAD v2.1

gnomAD v4.1

gnomAD-Canada

SpliceAI

OncoKB

COSMIC

Triaged references · 1 PMID not cited in assessment

28492532 ↗ Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. CLINVAR