22-36285117-G-C
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_002473.6(MYH9):c.5483+4C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.02 in 1,613,594 control chromosomes in the GnomAD database, including 387 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_002473.6 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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MYH9 | NM_002473.6 | c.5483+4C>G | splice_region_variant, intron_variant | Intron 38 of 40 | ENST00000216181.11 | NP_002464.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0152 AC: 2310AN: 152234Hom.: 26 Cov.: 33
GnomAD3 exomes AF: 0.0158 AC: 3933AN: 249710Hom.: 57 AF XY: 0.0158 AC XY: 2133AN XY: 135078
GnomAD4 exome AF: 0.0205 AC: 30014AN: 1461242Hom.: 361 Cov.: 32 AF XY: 0.0200 AC XY: 14564AN XY: 726922
GnomAD4 genome AF: 0.0152 AC: 2309AN: 152352Hom.: 26 Cov.: 33 AF XY: 0.0147 AC XY: 1095AN XY: 74496
ClinVar
Submissions by phenotype
not specified Benign:5
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This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
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5483+4C>G in Intron 38 of MYH9: This variant is not expected to have clinical si gnificance because it has been identified in 2.3% (163/7020) of European America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs56327920). -
not provided Benign:4
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Autosomal dominant nonsyndromic hearing loss 17 Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Kidney disorder Benign:1
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MYH9-related disorder Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at