chrX-148662021-A-G
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_002025.4(AFF2):c.294A>G(p.Pro98=) variant causes a synonymous change. The variant allele was found at a frequency of 0.000383 in 1,209,078 control chromosomes in the GnomAD database, including 1 homozygotes. There are 138 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 0.00023 ( 0 hom., 3 hem., cov: 23)
Exomes 𝑓: 0.00040 ( 1 hom. 135 hem. )
Consequence
AFF2
NM_002025.4 synonymous
NM_002025.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.64
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=-0.53).
BP6
?
Variant X-148662021-A-G is Benign according to our data. Variant chrX-148662021-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 728558.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000232 (26/111898) while in subpopulation NFE AF= 0.000432 (23/53190). AF 95% confidence interval is 0.000295. There are 0 homozygotes in gnomad4. There are 3 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
BS2
?
High Hemizygotes in GnomAd at 3 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AFF2 | NM_002025.4 | c.294A>G | p.Pro98= | synonymous_variant | 3/21 | ENST00000370460.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AFF2 | ENST00000370460.7 | c.294A>G | p.Pro98= | synonymous_variant | 3/21 | 5 | NM_002025.4 | P1 | |
AFF2 | ENST00000342251.7 | c.282A>G | p.Pro94= | synonymous_variant | 3/20 | 1 | |||
AFF2 | ENST00000370457.9 | c.294A>G | p.Pro98= | synonymous_variant | 3/20 | 1 | |||
AFF2 | ENST00000370458.5 | c.282A>G | p.Pro94= | synonymous_variant | 3/8 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.000232 AC: 26AN: 111898Hom.: 0 Cov.: 23 AF XY: 0.0000881 AC XY: 3AN XY: 34050
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GnomAD3 exomes AF: 0.000213 AC: 39AN: 183470Hom.: 1 AF XY: 0.000221 AC XY: 15AN XY: 67914
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GnomAD4 exome AF: 0.000398 AC: 437AN: 1097180Hom.: 1 Cov.: 30 AF XY: 0.000372 AC XY: 135AN XY: 362570
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
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Name
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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