rs755206033
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4BP6BS2_Supporting
The NM_004006.3(DMD):c.4721G>A(p.Arg1574His) variant causes a missense change. The variant allele was found at a frequency of 0.0000605 in 1,207,129 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 26 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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1574C) has been classified as Uncertain significance.
Frequency
Consequence
NM_004006.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DMD | NM_004006.3 | c.4721G>A | p.Arg1574His | missense_variant | 34/79 | ENST00000357033.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DMD | ENST00000357033.9 | c.4721G>A | p.Arg1574His | missense_variant | 34/79 | 1 | NM_004006.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000540 AC: 6AN: 111159Hom.: 0 Cov.: 22 AF XY: 0.0000598 AC XY: 2AN XY: 33433
GnomAD3 exomes AF: 0.0000880 AC: 16AN: 181824Hom.: 0 AF XY: 0.0000749 AC XY: 5AN XY: 66724
GnomAD4 exome AF: 0.0000611 AC: 67AN: 1095970Hom.: 0 Cov.: 29 AF XY: 0.0000663 AC XY: 24AN XY: 361890
GnomAD4 genome ? AF: 0.0000540 AC: 6AN: 111159Hom.: 0 Cov.: 22 AF XY: 0.0000598 AC XY: 2AN XY: 33433
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 18, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 27, 2020 | - - |
Uncertain significance, no assertion criteria provided | provider interpretation | Stanford Center for Inherited Cardiovascular Disease, Stanford University | Nov 02, 2016 | p.Arg1574His (c.4721G>A) in DMD Seen in a family with familial DCM in our center, with a likely pathogenic DSP variant. Testing done at Invitae. Given this is a missense change and is present at an appreciable frequency in ExAC (0.02%) we consider a variant of uncertain significance, probably benign. - |
Dilated cardiomyopathy 3B Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Duchenne muscular dystrophy;C0878544:Cardiomyopathy;C0917713:Becker muscular dystrophy;na:Dystrophin deficiency Benign:1
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | May 10, 2018 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 04, 2022 | 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. - |
Duchenne muscular dystrophy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at