rs535492772
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6BP7BS1
The NM_015404.4(WHRN):c.2112G>T(p.Leu704=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000601 in 1,614,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000055 ( 0 hom. )
Consequence
WHRN
NM_015404.4 synonymous
NM_015404.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -7.07
Genes affected
WHRN (HGNC:16361): (whirlin) This gene is thought to function in the organization and stabilization of sterocilia elongation and actin cystoskeletal assembly, based on studies of the related mouse gene. Mutations in this gene have been associated with autosomal recessive non-syndromic deafness and Usher Syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
?
Variant 9-114406479-C-A is Benign according to our data. Variant chr9-114406479-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 199138.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=1}.
BP7
?
Synonymous conserved (PhyloP=-7.07 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000105 (16/152310) while in subpopulation AMR AF= 0.000784 (12/15300). AF 95% confidence interval is 0.000452. There are 0 homozygotes in gnomad4. There are 5 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WHRN | NM_015404.4 | c.2112G>T | p.Leu704= | synonymous_variant | 9/12 | ENST00000362057.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WHRN | ENST00000362057.4 | c.2112G>T | p.Leu704= | synonymous_variant | 9/12 | 1 | NM_015404.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 152192Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000136 AC: 34AN: 250580Hom.: 0 AF XY: 0.000133 AC XY: 18AN XY: 135600
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GnomAD4 exome AF: 0.0000554 AC: 81AN: 1461786Hom.: 0 Cov.: 33 AF XY: 0.0000509 AC XY: 37AN XY: 727192
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GnomAD4 genome ? AF: 0.000105 AC: 16AN: 152310Hom.: 0 Cov.: 33 AF XY: 0.0000671 AC XY: 5AN XY: 74470
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 21, 2018 | This variant is associated with the following publications: (PMID: 23441107) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 12, 2014 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 19, 2023 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 29, 2015 | p.Leu704Leu in exon 9 of DFNB31: This variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located within the splice consensus sequence. This variant has been identified in 6/1156 2 of Latino chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.b roadinstitute.org}. - |
Computational scores
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Calibrated prediction
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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