2-99554354-G-A
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_001386135.1(AFF3):c.3516C>T(p.Tyr1172=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,614,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000034 ( 0 hom. )
Consequence
AFF3
NM_001386135.1 synonymous
NM_001386135.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.35
Genes affected
AFF3 (HGNC:6473): (ALF transcription elongation factor 3) This gene encodes a tissue-restricted nuclear transcriptional activator that is preferentially expressed in lymphoid tissue. Isolation of this protein initially defined a highly conserved LAF4/MLLT2 gene family of nuclear transcription factors that may function in lymphoid development and oncogenesis. In some ALL patients, this gene has been found fused to the gene for MLL. Multiple alternatively spliced transcript variants that encode different proteins have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BP6
?
Variant 2-99554354-G-A is Benign according to our data. Variant chr2-99554354-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3040901.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-1.36 with no splicing effect.
BS2
?
High AC in GnomAdExome at 17 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AFF3 | NM_001386135.1 | c.3516C>T | p.Tyr1172= | synonymous_variant | 24/25 | ENST00000672756.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AFF3 | ENST00000672756.2 | c.3516C>T | p.Tyr1172= | synonymous_variant | 24/25 | NM_001386135.1 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152182Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000676 AC: 17AN: 251440Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135900
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GnomAD4 exome AF: 0.0000342 AC: 50AN: 1461878Hom.: 0 Cov.: 32 AF XY: 0.0000275 AC XY: 20AN XY: 727240
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74348
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
AFF3-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 02, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at