chr16-89957654-G-A
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2
The NM_001242818.2(DEF8):c.366G>A(p.Glu122=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00199 in 1,558,710 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.010 ( 35 hom., cov: 33)
Exomes 𝑓: 0.0011 ( 27 hom. )
Consequence
DEF8
NM_001242818.2 synonymous
NM_001242818.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.70
Genes affected
DEF8 (HGNC:25969): (differentially expressed in FDCP 8 homolog) Predicted to enable metal ion binding activity. Predicted to be involved in lysosome localization; positive regulation of bone resorption; and positive regulation of ruffle assembly. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
Variant 16-89957654-G-A is Benign according to our data. Variant chr16-89957654-G-A is described in ClinVar as [Benign]. Clinvar id is 773059.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=1.7 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0105 (1599/152374) while in subpopulation AFR AF= 0.0363 (1510/41586). AF 95% confidence interval is 0.0348. There are 35 homozygotes in gnomad4. There are 724 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 35 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DEF8 | NM_001242818.2 | c.366G>A | p.Glu122= | synonymous_variant | 5/13 | ENST00000563594.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DEF8 | ENST00000563594.6 | c.366G>A | p.Glu122= | synonymous_variant | 5/13 | 1 | NM_001242818.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0105 AC: 1594AN: 152256Hom.: 35 Cov.: 33
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GnomAD3 exomes AF: 0.00247 AC: 409AN: 165910Hom.: 8 AF XY: 0.00161 AC XY: 142AN XY: 88294
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GnomAD4 exome AF: 0.00106 AC: 1497AN: 1406336Hom.: 27 Cov.: 31 AF XY: 0.000901 AC XY: 626AN XY: 694624
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GnomAD4 genome AF: 0.0105 AC: 1599AN: 152374Hom.: 35 Cov.: 33 AF XY: 0.00972 AC XY: 724AN XY: 74520
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at