chr2-99554396-C-T
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_001386135.1(AFF3):c.3474G>A(p.Ala1158=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,614,150 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00077 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 2 hom. )
Consequence
AFF3
NM_001386135.1 synonymous
NM_001386135.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.00
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 -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
Variant 2-99554396-C-T is Benign according to our data. Variant chr2-99554396-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2651182.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-1 with no splicing effect.
BS2
?
High AC in GnomAd at 118 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AFF3 | NM_001386135.1 | c.3474G>A | p.Ala1158= | synonymous_variant | 24/25 | ENST00000672756.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AFF3 | ENST00000672756.2 | c.3474G>A | p.Ala1158= | synonymous_variant | 24/25 | NM_001386135.1 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000776 AC: 118AN: 152154Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00100 AC: 252AN: 251466Hom.: 0 AF XY: 0.00112 AC XY: 152AN XY: 135918
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GnomAD4 exome AF: 0.00110 AC: 1608AN: 1461878Hom.: 2 Cov.: 32 AF XY: 0.00118 AC XY: 859AN XY: 727244
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GnomAD4 genome ? AF: 0.000775 AC: 118AN: 152272Hom.: 1 Cov.: 32 AF XY: 0.000618 AC XY: 46AN XY: 74456
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2022 | AFF3: BP4, BP7 - |
AFF3-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 05, 2019 | 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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BayesDel_noAF
Benign
Cadd
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Dann
Benign
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at