chr4-87137185-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001166693.3(AFF1):​c.*1484A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 227,866 control chromosomes in the GnomAD database, including 2,959 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.13 ( 1709 hom., cov: 32)
Exomes 𝑓: 0.16 ( 1250 hom. )

Consequence

AFF1
NM_001166693.3 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.130

Publications

11 publications found
Variant links:
Genes affected
AFF1 (HGNC:7135): (ALF transcription elongation factor 1) This gene encodes a member of the AF4/ lymphoid nuclear protein related to the Fragile X E syndrome (FRAXE) family of proteins, which have been implicated in human childhood lymphoblastic leukemia, fragile chromosome X intellectual disability, and ataxia. It is the prevalent mixed-lineage leukemia fusion gene associated with spontaneous acute lymphoblastic leukemia. Members of this family have three conserved domains: an N-terminal homology domain, an AF4/ lymphoid nuclear protein domain, and a C-terminal homology domain. The protein functions as a regulator of RNA polymerase II-mediated transcription through elongation and chromatin remodeling functions. Through RNA interference screens, this gene has been shown to promote the expression of CD133, a plasma membrane glycoprotein required for leukemia cell survival. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2017]

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AFF1NM_001166693.3 linkc.*1484A>T 3_prime_UTR_variant Exon 21 of 21 ENST00000395146.9 NP_001160165.1 P51825-2Q14C88

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AFF1ENST00000395146.9 linkc.*1484A>T 3_prime_UTR_variant Exon 21 of 21 2 NM_001166693.3 ENSP00000378578.4 P51825-2
AFF1ENST00000307808.10 linkc.*1484A>T 3_prime_UTR_variant Exon 20 of 20 1 ENSP00000305689.6 P51825-1
AFF1ENST00000544085.6 linkc.*1484A>T 3_prime_UTR_variant Exon 20 of 20 5 ENSP00000440843.3 P51825-3F5GXF9

Frequencies

GnomAD3 genomes
AF:
0.129
AC:
19673
AN:
152130
Hom.:
1710
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0392
Gnomad AMI
AF:
0.163
Gnomad AMR
AF:
0.135
Gnomad ASJ
AF:
0.319
Gnomad EAS
AF:
0.000577
Gnomad SAS
AF:
0.100
Gnomad FIN
AF:
0.128
Gnomad MID
AF:
0.184
Gnomad NFE
AF:
0.184
Gnomad OTH
AF:
0.159
GnomAD4 exome
AF:
0.161
AC:
12172
AN:
75618
Hom.:
1250
Cov.:
0
AF XY:
0.166
AC XY:
5811
AN XY:
34964
show subpopulations
African (AFR)
AF:
0.0419
AC:
150
AN:
3582
American (AMR)
AF:
0.118
AC:
271
AN:
2306
Ashkenazi Jewish (ASJ)
AF:
0.324
AC:
1532
AN:
4722
East Asian (EAS)
AF:
0.000189
AC:
2
AN:
10586
South Asian (SAS)
AF:
0.0991
AC:
63
AN:
636
European-Finnish (FIN)
AF:
0.147
AC:
71
AN:
482
Middle Eastern (MID)
AF:
0.157
AC:
71
AN:
452
European-Non Finnish (NFE)
AF:
0.191
AC:
8900
AN:
46538
Other (OTH)
AF:
0.176
AC:
1112
AN:
6314
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.497
Heterozygous variant carriers
0
454
908
1362
1816
2270
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
20
40
60
80
100
<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
AF:
0.129
AC:
19666
AN:
152248
Hom.:
1709
Cov.:
32
AF XY:
0.125
AC XY:
9314
AN XY:
74444
show subpopulations
African (AFR)
AF:
0.0391
AC:
1625
AN:
41552
American (AMR)
AF:
0.135
AC:
2065
AN:
15300
Ashkenazi Jewish (ASJ)
AF:
0.319
AC:
1107
AN:
3468
East Asian (EAS)
AF:
0.000771
AC:
4
AN:
5190
South Asian (SAS)
AF:
0.100
AC:
484
AN:
4824
European-Finnish (FIN)
AF:
0.128
AC:
1352
AN:
10598
Middle Eastern (MID)
AF:
0.187
AC:
55
AN:
294
European-Non Finnish (NFE)
AF:
0.184
AC:
12492
AN:
67994
Other (OTH)
AF:
0.157
AC:
333
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
840
1681
2521
3362
4202
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
214
428
642
856
1070
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.153
Hom.:
273
Bravo
AF:
0.128
Asia WGS
AF:
0.0540
AC:
189
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.50
CADD
Benign
5.8
DANN
Benign
0.70
PhyloP100
0.13
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs17703261; hg19: chr4-88058337; COSMIC: COSV57120449; COSMIC: COSV57120449; API