rs115623280
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_004408.4(DNM1):c.1905+17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00174 in 1,614,152 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0089 ( 23 hom., cov: 32)
Exomes 𝑓: 0.00099 ( 23 hom. )
Consequence
DNM1
NM_004408.4 intron
NM_004408.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.340
Genes affected
DNM1 (HGNC:2972): (dynamin 1) This gene encodes a member of the dynamin subfamily of GTP-binding proteins. The encoded protein possesses unique mechanochemical properties used to tubulate and sever membranes, and is involved in clathrin-mediated endocytosis and other vesicular trafficking processes. Actin and other cytoskeletal proteins act as binding partners for the encoded protein, which can also self-assemble leading to stimulation of GTPase activity. More than sixty highly conserved copies of the 3' region of this gene are found elsewhere in the genome, particularly on chromosomes Y and 15. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BP6
?
Variant 9-128247952-C-T is Benign according to our data. Variant chr9-128247952-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 382866.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00887 (1351/152288) while in subpopulation AFR AF= 0.0308 (1279/41532). AF 95% confidence interval is 0.0294. There are 23 homozygotes in gnomad4. There are 599 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 23 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNM1 | NM_004408.4 | c.1905+17C>T | intron_variant | ENST00000372923.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNM1 | ENST00000372923.8 | c.1905+17C>T | intron_variant | 1 | NM_004408.4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00888 AC: 1351AN: 152170Hom.: 23 Cov.: 32
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GnomAD3 exomes AF: 0.00243 AC: 610AN: 251446Hom.: 12 AF XY: 0.00161 AC XY: 219AN XY: 135892
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GnomAD4 exome AF: 0.000993 AC: 1452AN: 1461864Hom.: 23 Cov.: 31 AF XY: 0.000864 AC XY: 628AN XY: 727234
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GnomAD4 genome ? AF: 0.00887 AC: 1351AN: 152288Hom.: 23 Cov.: 32 AF XY: 0.00805 AC XY: 599AN XY: 74456
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 20, 2016 | 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. - |
Developmental and epileptic encephalopathy, 31 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Apr 19, 2017 | - - |
Computational scores
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Calibrated prediction
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Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at