0%
ABL1c.908-16G>AUncertain significance
Print report
Variant interpretation report

ABL1 c.908-16G>A, p.?

NM_005157.4:c.908-16G>A NP_005148.2:p.? View identifiers
Classification
Uncertain significance

Variant description:

No variant summary was recorded for this case.

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

Uncertain.The recorded classification is uncertain significance.

In plain language

Gene-level background from the recorded interpretation.

About ABL1

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: 1
Pathogenic criteria applied · 1
PM2Supporting
PM2 · supporting

This variant is rare in population databases. In gnomAD v2.1 the allele frequency is 0.00082% (2/244756), and in gnomAD v4.1 the allele frequency is 0.00169% (27/1600974), both below the 0.1% threshold used for PM2 in this workflow.

Benign criteria applied · 1
BP7Supporting
BP7 · supporting

This intronic variant is located at c.908-16, outside the canonical splice region, and SpliceAI predicts no significant splice impact with a maximum delta score of 0.01. These findings support BP7.

Recorded classification: Uncertain significance

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, BP7 supporting; combination = 1 supporting + 1 supporting benign, which maps to VUS because the evidence is conflicting.

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
27 / 1,600,974 alleles

gnomAD v4.1: 27 / 1,600,974 alleles. Recorded AF 1.68647e-05. Recorded homozygote count 0.

gnomAD 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).

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

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

Applied · BP7 → SpliceAI ↗
ClinVar submissions
1 reported laboratory submissions

1 Likely benign.

Context only ClinVar ↗
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.

28 criteria with recorded statuses: 2 met · 4 not met · 11 not assessed · 11 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic
PVS1PS1PS2PS3PS4PM1PM2PM3PM4PM5PM6PP1PP2PP3PP4PP5
Benign
BA1BS1BS2BS3BS4BP1BP2BP3BP4BP5BP6BP7
Met Not met Not assessed Not applicable

The ABL1 c.908-16G>A (p.?) variant has been reported in ClinVar as likely benign with single-submitter review status.

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.

SpliceAI predicts no significant splice effect for this intronic change, with a maximum delta score of 0.01, which supports a benign computational interpretation.

Met · 2

PM2 SupportingThis variant is rare in population databases. In gnomAD v2.1 the allele frequency is 0.00082% (2/244756), and in gnomAD v4.1 the allele frequency is 0.00169% (27/1600974), both below the 0.1% threshold used for PM2 in this workflow. Details ▾Hide ▴
Rule
Population frequency below PM2 threshold
Evidence considered
  • gnomAD v2.1 AF 8.1714e-06
  • gnomAD v4.1 AF 1.68647e-05
Sources
gnomad_v2 ↗gnomad_v4 ↗
BP7 SupportingThis intronic variant is located at c.908-16, outside the canonical splice region, and SpliceAI predicts no significant splice impact with a maximum delta score of 0.01. These findings support BP7. Details ▾Hide ▴
Rule
Intronic variant outside canonical splice region with no predicted splice impact
Evidence considered
  • Intronic position c.908-16
  • SpliceAI max delta score 0.01
Sources
spliceai ↗

Not met · 4 · evaluated, threshold not reached

PVS1 ABL1 loss of function is considered an eligible disease mechanism in the generic PVS1 gate, but this variant is intronic at c.908-16, is outside the canonical +/-1,2 splice sites, and does not fall into the generic null-variant buckets for PVS1. SpliceAI also predicts no significant splice impact (max delta score 0.01), so current evidence does not support PVS1. Details ▾Hide ▴
Rule
Generic PVS1 fallback not triggered for non-canonical intronic variant without predicted splice disruption
Evidence considered
  • Generic PVS1 eligibility for ABL1 loss of function
  • Variant is outside canonical splice consensus
  • SpliceAI max delta score 0.01
Sources
pvs1_gene_contextpvs1_variant_assessmentpvs1_generic_framework ↗spliceai ↗
PP3 Available computational evidence does not support a damaging effect. SpliceAI predicts no significant splice impact with a maximum delta score of 0.01, and no REVEL, BayesDel, or HCI prior result was available for this intronic variant. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta score 0.01
  • REVEL not available
  • BayesDel not available
  • HCI prior not available
Sources
spliceai ↗
BA1 The population frequency does not meet the BA1 benign stand-alone threshold. The highest observed overall frequency is 0.00169% in gnomAD v4.1, which is below the 1% BA1 threshold. Details ▾Hide ▴
Rule
Population frequency below BA1 threshold
Evidence considered
  • gnomAD v4.1 AF 1.68647e-05
Sources
gnomad_v4 ↗
BS1 The population frequency does not reach the BS1 threshold. The highest observed overall frequency is 0.00169% in gnomAD v4.1, which is below the 0.3% BS1 threshold. Details ▾Hide ▴
Rule
Population frequency below BS1 threshold
Evidence considered
  • gnomAD v4.1 AF 1.68647e-05
Sources
gnomad_v4 ↗

Not assessed · 11 · no assessment recorded

PS2 No confirmed de novo occurrence with parental confirmation was identified for this variant. Details ▾Hide ▴
Evidence considered
  • No de novo evidence identified in available records
Still missing
  • Parental testing or a published de novo case for this exact variant
Sources
clinvar ↗
PS3 No well-established functional study or RNA assay was identified for this exact variant, so PS3 cannot be applied. Details ▾Hide ▴
Evidence considered
  • No exact-variant functional evidence located
Still missing
  • Variant-specific RNA study or validated functional assay
Sources
clinvar ↗spliceai ↗
PS4 No case-control enrichment or multiple independent affected observations were identified for this variant. Details ▾Hide ▴
Evidence considered
  • Single ClinVar submitter
  • Population presence in gnomAD
Still missing
  • Affected-case counts or case-control data for the exact variant
Sources
clinvar ↗gnomad_v2 ↗gnomad_v4 ↗
PM6 No assumed de novo occurrence without full parental confirmation was identified for this variant. Details ▾Hide ▴
Evidence considered
  • No de novo evidence identified
Still missing
  • Published or submitted presumed de novo case for the exact variant
Sources
clinvar ↗
PP1 No segregation data were identified for this variant. Details ▾Hide ▴
Evidence considered
  • No segregation evidence identified
Still missing
  • Family segregation data
Sources
clinvar ↗
PP4 No phenotype information was available to determine whether the clinical presentation is highly specific for a disease caused by ABL1. Details ▾Hide ▴
Still missing
  • Phenotype and clinical correlation data
BS2 No evidence was identified showing this variant in healthy adult individuals in a manner sufficient for BS2. Details ▾Hide ▴
Evidence considered
  • Population presence alone is insufficient for BS2
Still missing
  • Well-documented unaffected carrier observations appropriate for the disease context
Sources
gnomad_v2 ↗gnomad_v4 ↗
BS3 No well-established functional study showing no damaging effect was identified for this variant. Details ▾Hide ▴
Evidence considered
  • No direct benign functional study identified
Still missing
  • Variant-specific negative functional or RNA assay
Sources
spliceai ↗
BS4 No non-segregation data were identified for this variant. Details ▾Hide ▴
Evidence considered
  • No family non-segregation evidence identified
Still missing
  • Family data showing lack of segregation
Sources
clinvar ↗
BP2 No phase data were identified to determine whether this variant occurs in cis or in trans with another variant. Details ▾Hide ▴
Still missing
  • Phase information
BP5 No alternate molecular explanation was identified for an observed phenotype, so BP5 was not assessed. Details ▾Hide ▴
Still missing
  • Phenotype-level molecular differential diagnosis
Not applicable · 11· recorded as not applicable Show reasons ▾Hide reasons ▴
PS1 N/AThis criterion applies to a different nucleotide change causing the same amino acid substitution. This intronic variant has no defined amino acid change, so PS1 is not applicable. Details ▾Hide ▴
Evidence considered
  • Protein consequence remains p.?
PM1 N/APM1 is used for variants in a critical functional domain or mutational hot spot without benign variation. This intronic variant does not map to a protein residue or domain, so PM1 is not applicable. Details ▾Hide ▴
Evidence considered
  • Intronic variant with no protein residue assignment
PM3 N/APM3 applies to recessive disease with pathogenic variants observed in trans. No recessive trans data were identified for this variant, and this criterion is not applicable here. Details ▾Hide ▴

No further detail was recorded.

PM4 N/APM4 applies to protein length changes from in-frame deletions/insertions or stop-loss variants. This intronic single-nucleotide variant does not have that effect. Details ▾Hide ▴

No further detail was recorded.

PM5 N/APM5 uses same-residue missense comparator logic. This variant is intronic with no amino acid residue context, and the PM5 candidate review did not support classic PM5 use. Details ▾Hide ▴
Evidence considered
  • No residue-based comparator context
Sources
pm5_candidates
PP2 N/APP2 applies to missense variants in genes with low benign missense variation and a pathogenic missense mechanism. This intronic variant is not a missense change. Details ▾Hide ▴

No further detail was recorded.

PP5 N/APP5 was not used because current ACMG/AMP practice does not rely on an external assertion alone as evidence for pathogenicity. Details ▾Hide ▴
Evidence considered
  • ClinVar contains a single submitter assertion only
Sources
clinvar ↗28492532
BP1 N/ABP1 applies to missense variants in genes where truncating variants are primarily pathogenic. This intronic variant is not a missense change. Details ▾Hide ▴

No further detail was recorded.

BP3 N/ABP3 applies to in-frame variants in repetitive regions without known function. This intronic single-nucleotide variant does not fit that criterion. Details ▾Hide ▴

No further detail was recorded.

BP4 N/AFor this intronic variant, benign computational splice evidence is captured more specifically under BP7. BP4 was not applied separately to avoid double counting the same in silico evidence. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta score 0.01
Sources
spliceai ↗
BP6 N/ABP6 was not used because current ACMG/AMP practice does not rely on an external assertion alone as evidence for benignity. Details ▾Hide ▴
Evidence considered
  • Single ClinVar benign assertion
Sources
clinvar ↗28492532

Identifiers

Gene
ABL1
Transcript
NM_005157.4
Coding (HGVS c.)
NM_005157.4:c.908-16G>A
Protein (HGVS p.)
NP_005148.2:p.?
GRCh38
chr9:130872844 G>A
GRCh37
chr9:133748231 G>A
ClinVar
4763580

Gene diagram

Every interpreted variant in ABL1, mapped onto the exon structure of NM_005157.4. Select a row to find it on the plot.

ABL1NM_005157.4
Fetching transcript structure from UCSC…
gnomAD v4.1 27 / 1,600,974 alleles AF 1.69e-05 · 0 homozygotes · FAF 1.54e-05
gnomAD v2.1 2 / 244,756 alleles AF 8.17e-06 · 0 homozygotes

By genetic ancestry

gnomAD v4.1

AF 1.7e-05 · 27 / 1,600,974 alleles · 0 hom · FAF 1.5e-05
European (non-Finnish)26 / 1,171,134 2.2e-05
South Asian1 / 90,118 1.1e-05
0 alternate alleles recorded in 8 other groups: Remaining individuals, Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, Ashkenazi Jewish, African/African American.

gnomAD v2.1

AF 8.2e-06 · 2 / 244,756 alleles · 0 hom
South Asian1 / 29,656 3.4e-05
European (non-Finnish)1 / 110,438 9.1e-06
0 alternate alleles recorded in 6 other groups: African/African American, Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), Remaining individuals.

Statements

gnomAD 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.

gnomAD 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).

SpliceAI and Pangolin

SpliceAI acceptor lossat -46 bp
0.010
SpliceAI acceptor gainat +13 bp
0.000
SpliceAI donor lossat -124 bp
0.000
SpliceAI donor gainat +436 bp
0.000
Pangolin splice lossmagnitude shown
-0.010
Pangolin splice gain
0.000

Other predictors

REVEL
Not available
BayesDel
Not available

How the predictions were used

BP7 SupportingThis intronic variant is located at c.908-16, outside the canonical splice region, and SpliceAI predicts no significant splice impact with a maximum delta score of 0.01. These findings support BP7. Details ▾Hide ▴
Rule
Intronic variant outside canonical splice region with no predicted splice impact
Evidence considered
  • Intronic position c.908-16
  • SpliceAI max delta score 0.01
Sources
spliceai ↗
PP3 Available computational evidence does not support a damaging effect. SpliceAI predicts no significant splice impact with a maximum delta score of 0.01, and no REVEL, BayesDel, or HCI prior result was available for this intronic variant. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta score 0.01
  • REVEL not available
  • BayesDel not available
  • HCI prior not available
Sources
spliceai ↗
BP4 N/AFor this intronic variant, benign computational splice evidence is captured more specifically under BP7. BP4 was not applied separately to avoid double counting the same in silico evidence. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta score 0.01
Sources
spliceai ↗

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
    No paper-specific finding is recorded.
    PMID 28492532 ↗

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

gnomAD v4.1 27 / 1,600,974 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= 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.

gnomAD 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).

ClinVar

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

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).