Classification rationale

PM2 BP7 VUS

ABL1 c.908-16G>A

The ABL1 c.908-16G>A (p.?) variant has been reported in ClinVar as likely benign with single-submitter review status.¹ This variant is present at very low frequency in population databases, with allele frequencies of 0.00082% in gnomAD v2.1 and 0.00169% in gnomAD v4.1, both below the 0.1% PM2 threshold used in this workflow.² SpliceAI predicts no significant splice effect for this intronic change, with a maximum delta score of 0.01, which supports a benign computational interpretation.³

PM2 + BP7 → VUS

1 clinvar ↗

2 gnomad_v2 ↗gnomad_v4 ↗

3 spliceai ↗

Gene diagram · NM_005157.4 · variants mapped to exon structure

ABL1 NM_005157.4

Fetching transcript structure from UCSC…

Applied criteria · 2 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

gnomAD v4.1

gnomAD v2.1

v4.1

This variant is present in gnomAD v4.1 (AF= 1.68647e-05; MAF= 0.00169%, 27/1600974 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 2.22007e-05; MAF= 0.00222%, 26/1171134 alleles, homozygotes = 0); grpmax FAF= 1.544e-05.

v2.1

This variant is present in gnomAD v2.1 (AF= 8.1714e-06; MAF= 0.00082%, 2/244756 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 3.372e-05; MAF= 0.00337%, 1/29656 alleles, homozygotes = 0).

Allele frequency by ancestry

three datasets · side by side

gnomAD v4.1

0.0017% · 27 / 1,600,974
0 hom · FAF 0.0015%

European (non-Finnish) 26 / 1,171,134	0.0022%
South Asian 1 / 90,118	0.0011%

+ 8 not observed (Remaining individuals, Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, Ashkenazi Jewish, African/African American)

gnomAD v2.1

0.00082% · 2 / 244,756
0 hom

South Asian 1 / 29,656	0.0034%
European (non-Finnish) 1 / 110,438	0.00091%

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

gnomAD v4 ↗ gnomAD v2 ↗

ClinVar

This variant has been reported in ClinVar as Likely benign (1 clinical laboratory). (ClinVarID = 4763580)

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

6Sources

ClinVar

gnomAD v2.1

gnomAD v4.1

SpliceAI

OncoKB

COSMIC

Triaged references · 1 PMID not cited in assessment

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