rs2070818
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000117.3(EMD):āc.445G>Cā(p.Asp149His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000177 in 1,210,652 control chromosomes in the GnomAD database, including 1 homozygotes. There are 69 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Consequence
NM_000117.3 missense
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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EMD | NM_000117.3 | c.445G>C | p.Asp149His | missense_variant | 5/6 | ENST00000369842.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EMD | ENST00000369842.9 | c.445G>C | p.Asp149His | missense_variant | 5/6 | 1 | NM_000117.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000240 AC: 27AN: 112487Hom.: 0 Cov.: 24 AF XY: 0.000260 AC XY: 9AN XY: 34645
GnomAD3 exomes AF: 0.000464 AC: 85AN: 183322Hom.: 0 AF XY: 0.000456 AC XY: 31AN XY: 67916
GnomAD4 exome AF: 0.000171 AC: 188AN: 1098113Hom.: 1 Cov.: 32 AF XY: 0.000165 AC XY: 60AN XY: 363521
GnomAD4 genome ? AF: 0.000231 AC: 26AN: 112539Hom.: 0 Cov.: 24 AF XY: 0.000259 AC XY: 9AN XY: 34707
ClinVar
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 22, 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. - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | May 25, 2022 | Variant summary: EMD c.445G>C (p.Asp149His) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00044 in 205102 control chromosomes (gnomAD), predominantly at a frequency of 0.0058 within the East Asian subpopulation in the gnomAD database, including 31 hemizygotes. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 6 fold of the estimated maximal expected allele frequency for a pathogenic variant in EMD causing Emery-Dreifuss Muscular Dystrophy phenotype (0.001), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. Six ClinVar submitters have assessed the variant since 2014: one classified the variant as likely benign and five as benign. Based on the evidence outlined above, the variant was classified as benign. - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 05, 2017 | - - |
not provided Benign:2
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Emery-Dreifuss muscular dystrophy Benign:1
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Cardiomyopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego | Apr 04, 2017 | - - |
X-linked Emery-Dreifuss muscular dystrophy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 08, 2021 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at