rs782061626
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_000117.3(EMD):c.400-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000126 in 1,210,356 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 40 hemizygotes in GnomAD. 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 0.000062 ( 0 hom., 2 hem., cov: 24)
Exomes 𝑓: 0.00013 ( 0 hom. 38 hem. )
Consequence
EMD
NM_000117.3 intron
NM_000117.3 intron
Scores
2
Splicing: ADA: 0.00003167
2
Clinical Significance
Conservation
PhyloP100: -0.448
Genes affected
EMD (HGNC:3331): (emerin) Emerin is a serine-rich nuclear membrane protein and a member of the nuclear lamina-associated protein family. It mediates membrane anchorage to the cytoskeleton. Dreifuss-Emery muscular dystrophy is an X-linked inherited degenerative myopathy resulting from mutation in the emerin gene. [provided by RefSeq, Jul 2008]
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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=-0.86).
BP6
Variant X-154380744-C-T is Benign according to our data. Variant chrX-154380744-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 227353.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=1}. Variant chrX-154380744-C-T is described in Lovd as [Benign]. Variant chrX-154380744-C-T is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.000132 (145/1097785) while in subpopulation NFE AF= 0.00016 (135/842127). AF 95% confidence interval is 0.000138. There are 0 homozygotes in gnomad4_exome. There are 38 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Hemizygotes in GnomAd4 at 2 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EMD | NM_000117.3 | c.400-9C>T | intron_variant | ENST00000369842.9 | NP_000108.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
EMD | ENST00000369842.9 | c.400-9C>T | intron_variant | 1 | NM_000117.3 | ENSP00000358857.4 |
Frequencies
GnomAD3 genomes AF: 0.0000622 AC: 7AN: 112571Hom.: 0 Cov.: 24 AF XY: 0.0000576 AC XY: 2AN XY: 34709
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GnomAD3 exomes AF: 0.0000819 AC: 15AN: 183100Hom.: 0 AF XY: 0.0000590 AC XY: 4AN XY: 67818
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GnomAD4 exome AF: 0.000132 AC: 145AN: 1097785Hom.: 0 Cov.: 32 AF XY: 0.000105 AC XY: 38AN XY: 363325
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GnomAD4 genome AF: 0.0000622 AC: 7AN: 112571Hom.: 0 Cov.: 24 AF XY: 0.0000576 AC XY: 2AN XY: 34709
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:8
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:2
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 03, 2017 | - - |
not specified Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 26, 2015 | c.400-9C>T in intron 5 of EMD: This variant is not expected to have clinical sig nificance because a C>T change at this position does not diverge from the splice consensus sequence and is therefore unlikely to impact splicing. In addition, i t has been identified in 10/47376 European chromosomes including 3 hemizygous ma les by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org). - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 30, 2017 | 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. - |
X-linked Emery-Dreifuss muscular dystrophy Benign:2
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 09, 2024 | - - |
Emery-Dreifuss muscular dystrophy Benign:1
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 08, 2020 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at