rs377223643
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6BS2_Supporting
The NM_004006.3(DMD):c.1603-4C>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000839 in 1,192,018 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_004006.3 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DMD | NM_004006.3 | c.1603-4C>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000357033.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DMD | ENST00000357033.9 | c.1603-4C>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_004006.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000895 AC: 1AN: 111698Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 33888
GnomAD3 exomes AF: 0.0000166 AC: 3AN: 180308Hom.: 0 AF XY: 0.0000154 AC XY: 1AN XY: 65086
GnomAD4 exome AF: 0.00000833 AC: 9AN: 1080320Hom.: 0 Cov.: 28 AF XY: 0.00000577 AC XY: 2AN XY: 346346
GnomAD4 genome ? AF: 0.00000895 AC: 1AN: 111698Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 33888
ClinVar
Submissions by phenotype
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 07, 2015 | The c.1603-4C>G intronic variant results from a C to G substitution 4 nucleotides upstream from coding exon 14 in the DMD gene. This nucleotide position is poorly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is not predicted to have any significant effect on this splice acceptor site; however, direct evidence is unavailable. Since supporting evidence for this variant is limited at this time, its clinical significance is unclear. - |
Duchenne muscular dystrophy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 31, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at