chrX-31657979-G-A
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_004006.3(DMD):c.8027+11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 1,201,414 control chromosomes in the GnomAD database, including 50,207 homozygotes. There are 137,658 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_004006.3 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DMD | ENST00000357033.9 | c.8027+11C>T | intron_variant | Intron 54 of 78 | 1 | NM_004006.3 | ENSP00000354923.3 |
Frequencies
GnomAD3 genomes AF: 0.331 AC: 36514AN: 110243Hom.: 4449 Cov.: 22 AF XY: 0.329 AC XY: 10700AN XY: 32547
GnomAD3 exomes AF: 0.332 AC: 60352AN: 181665Hom.: 6516 AF XY: 0.342 AC XY: 22773AN XY: 66529
GnomAD4 exome AF: 0.352 AC: 383534AN: 1091114Hom.: 45758 Cov.: 29 AF XY: 0.355 AC XY: 126944AN XY: 357886
GnomAD4 genome AF: 0.331 AC: 36518AN: 110300Hom.: 4449 Cov.: 22 AF XY: 0.329 AC XY: 10714AN XY: 32612
ClinVar
Submissions by phenotype
not specified Benign:7
c.8027+11C>T in intron 54 of DMD: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus seq uence. It has been identified in 35.1% (2361/6725) of European American chromoso mes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs .washington.edu/EVS; dbSNP rs2270672). -
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Variant summary: DMD c.8027+11C>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.34 in 198201 control chromosomes in the gnomAD database, including 7231 homozygotes and 25267 hemizygotes. The observed variant frequency is approximately 30-fold above the estimated maximal expected allele frequency for a pathogenic variant in DMD causing Dystrophiopathies phenotype (0.011), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.8027+11C>T in individuals affected with Dystrophiopathies and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign. -
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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Dilated cardiomyopathy 3B Benign:2
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. -
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not provided Benign:2
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Duchenne muscular dystrophy Benign:2
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Duchenne muscular dystrophy;C0878544:Cardiomyopathy;C0917713:Becker muscular dystrophy;na:Dystrophin deficiency Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at