rs340638
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The ENST00000307808.10(AFF1):c.-356C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 1,179,678 control chromosomes in the GnomAD database, including 333,283 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 0.63 ( 33374 hom., cov: 35)
Exomes 𝑓: 0.76 ( 299909 hom. )
Consequence
AFF1
ENST00000307808.10 5_prime_UTR
ENST00000307808.10 5_prime_UTR
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -4.26
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 made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AFF1 | NM_001166693.3 | c.39-39114C>T | intron_variant | ENST00000395146.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AFF1 | ENST00000395146.9 | c.39-39114C>T | intron_variant | 2 | NM_001166693.3 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.633 AC: 96329AN: 152104Hom.: 33371 Cov.: 35
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GnomAD4 exome AF: 0.760 AC: 780567AN: 1027456Hom.: 299909 Cov.: 60 AF XY: 0.762 AC XY: 368360AN XY: 483648
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GnomAD4 genome ? AF: 0.633 AC: 96351AN: 152222Hom.: 33374 Cov.: 35 AF XY: 0.634 AC XY: 47169AN XY: 74428
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ClinVar
Not reported inComputational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at