rs76308107
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_001375834.1(WIPF1):āc.339C>Gā(p.Ser113=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,612,036 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.0056 ( 11 hom., cov: 32)
Exomes š: 0.00055 ( 5 hom. )
Consequence
WIPF1
NM_001375834.1 synonymous
NM_001375834.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.56
Genes affected
WIPF1 (HGNC:12736): (WAS/WASL interacting protein family member 1) This gene encodes a protein that plays an important role in the organization of the actin cytoskeleton. The encoded protein binds to a region of Wiskott-Aldrich syndrome protein that is frequently mutated in Wiskott-Aldrich syndrome, an X-linked recessive disorder. Impairment of the interaction between these two proteins may contribute to the disease. Two transcript variants encoding the same protein have been identified for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP6
Variant 2-174575223-G-C is Benign according to our data. Variant chr2-174575223-G-C is described in ClinVar as [Benign]. Clinvar id is 472921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=2.56 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00564 (858/152224) while in subpopulation AFR AF= 0.02 (829/41514). AF 95% confidence interval is 0.0188. There are 11 homozygotes in gnomad4. There are 401 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 11 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WIPF1 | NM_001375834.1 | c.339C>G | p.Ser113= | synonymous_variant | 4/8 | ENST00000679041.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WIPF1 | ENST00000679041.1 | c.339C>G | p.Ser113= | synonymous_variant | 4/8 | NM_001375834.1 | P3 | ||
ENST00000442996.1 | n.217+27746G>C | intron_variant, non_coding_transcript_variant | 1 | ||||||
ENST00000454203.1 | upstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.00562 AC: 855AN: 152106Hom.: 11 Cov.: 32
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GnomAD3 exomes AF: 0.00145 AC: 358AN: 247622Hom.: 2 AF XY: 0.000970 AC XY: 130AN XY: 134042
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GnomAD4 exome AF: 0.000551 AC: 805AN: 1459812Hom.: 5 Cov.: 32 AF XY: 0.000426 AC XY: 309AN XY: 725972
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GnomAD4 genome AF: 0.00564 AC: 858AN: 152224Hom.: 11 Cov.: 32 AF XY: 0.00539 AC XY: 401AN XY: 74422
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Wiskott-Aldrich syndrome 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
WIPF1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 29, 2019 | This variant is classified as 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
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