5-132934546-G-GTGT
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PM4_SupportingBS2
The ENST00000265343.10(AFF4):c.516_518dupACA(p.Glu172_His173insGln) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.0000192 in 1,614,158 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000021 ( 1 hom. )
Consequence
AFF4
ENST00000265343.10 disruptive_inframe_insertion
ENST00000265343.10 disruptive_inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.21
Publications
0 publications found
Genes affected
AFF4 (HGNC:17869): (ALF transcription elongation factor 4) The protein encoded by this gene belongs to the AF4 family of transcription factors involved in leukemia. It is a component of the positive transcription elongation factor b (P-TEFb) complex. A chromosomal translocation involving this gene and MLL gene on chromosome 11 is found in infant acute lymphoblastic leukemia with ins(5;11)(q31;q31q23). [provided by RefSeq, Oct 2011]
AFF4 Gene-Disease associations (from GenCC):
- cognitive impairment - coarse facies - heart defects - obesity - pulmonary involvement - short stature - skeletal dysplasia syndromeInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Illumina
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -3 ACMG points.
PM4
Nonframeshift variant in NON repetitive region in ENST00000265343.10. Strenght limited to Supporting due to length of the change: 1aa.
BS2
High AC in GnomAdExome4 at 30 AD gene.
Variant Effect in Transcripts
ACMG analysis was done for transcript: ENST00000265343.10. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| AFF4 | NM_014423.4 | MANE Select | c.516_518dupACA | p.Glu172_His173insGln | disruptive_inframe_insertion | Exon 3 of 21 | NP_055238.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| AFF4 | ENST00000265343.10 | TSL:1 MANE Select | c.516_518dupACA | p.Glu172_His173insGln | disruptive_inframe_insertion | Exon 3 of 21 | ENSP00000265343.5 | ||
| AFF4 | ENST00000378595.7 | TSL:1 | c.516_518dupACA | p.Glu172_His173insGln | disruptive_inframe_insertion | Exon 3 of 13 | ENSP00000367858.3 | ||
| AFF4 | ENST00000465484.1 | TSL:1 | n.775_777dupACA | non_coding_transcript_exon | Exon 3 of 5 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152150Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152150
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.0000205 AC: 30AN: 1461890Hom.: 1 Cov.: 31 AF XY: 0.0000165 AC XY: 12AN XY: 727244 show subpopulations
GnomAD4 exome
AF:
AC:
30
AN:
1461890
Hom.:
Cov.:
31
AF XY:
AC XY:
12
AN XY:
727244
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
AC:
28
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
2
AN:
1112008
Other (OTH)
AF:
AC:
0
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.473
Heterozygous variant carriers
0
2
4
5
7
9
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Exome Hom
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome 0.00000657 AC: 1AN: 152268Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74464 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
AF:
AC:
1
AN:
152268
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74464
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
41554
American (AMR)
AF:
AC:
0
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5184
South Asian (SAS)
AF:
AC:
0
AN:
4828
European-Finnish (FIN)
AF:
AC:
0
AN:
10604
Middle Eastern (MID)
AF:
AC:
1
AN:
294
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68026
Other (OTH)
AF:
AC:
0
AN:
2108
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
ClinVar submissions as Germline
Significance:Uncertain significance
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
-
2
-
not provided (2)
-
1
-
Cognitive impairment - coarse facies - heart defects - obesity - pulmonary involvement - short stature - skeletal dysplasia syndrome (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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