rs782673472
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_002025.4(AFF2):c.47+16T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,208,723 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 22 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 24)
Exomes 𝑓: 0.000039 ( 0 hom. 21 hem. )
Consequence
AFF2
NM_002025.4 intron
NM_002025.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.334
Genes affected
AFF2 (HGNC:3776): (ALF transcription elongation factor 2) This gene encodes a putative transcriptional activator that is a member of the AF4\FMR2 gene family. This gene is associated with the folate-sensitive fragile X E locus on chromosome X. A repeat polymorphism in the fragile X E locus results in silencing of this gene causing Fragile X E syndrome. Fragile X E syndrome is a form of nonsyndromic X-linked cognitive disability. In addition, this gene contains 6-25 GCC repeats that are expanded to >200 repeats in the disease state. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Jul 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
Variant X-148501160-T-C is Benign according to our data. Variant chrX-148501160-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 210101.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0000178 (2/112325) while in subpopulation SAS AF= 0.000745 (2/2686). AF 95% confidence interval is 0.000131. There are 0 homozygotes in gnomad4. There are 1 alleles in male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.
BS2
High Hemizygotes in GnomAdExome4 at 21 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AFF2 | NM_002025.4 | c.47+16T>C | intron_variant | ENST00000370460.7 | NP_002016.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AFF2 | ENST00000370460.7 | c.47+16T>C | intron_variant | 5 | NM_002025.4 | ENSP00000359489.2 | ||||
AFF2 | ENST00000342251.7 | c.47+16T>C | intron_variant | 1 | ENSP00000345459.4 | |||||
AFF2 | ENST00000370457.9 | c.47+16T>C | intron_variant | 1 | ENSP00000359486.6 | |||||
AFF2 | ENST00000370458.5 | c.47+16T>C | intron_variant | 1 | ENSP00000359487.1 |
Frequencies
GnomAD3 genomes AF: 0.0000178 AC: 2AN: 112274Hom.: 0 Cov.: 24 AF XY: 0.0000290 AC XY: 1AN XY: 34442
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GnomAD3 exomes AF: 0.0000832 AC: 15AN: 180250Hom.: 0 AF XY: 0.000105 AC XY: 7AN XY: 66490
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GnomAD4 exome AF: 0.0000392 AC: 43AN: 1096398Hom.: 0 Cov.: 30 AF XY: 0.0000580 AC XY: 21AN XY: 362020
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GnomAD4 genome AF: 0.0000178 AC: 2AN: 112325Hom.: 0 Cov.: 24 AF XY: 0.0000290 AC XY: 1AN XY: 34503
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jul 17, 2015 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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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