10-99877160-C-T
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2
The NM_015221.4(DNMBP):c.4725G>A(p.Glu1575=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0225 in 1,609,802 control chromosomes in the GnomAD database, including 435 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).
Frequency
Genomes: 𝑓 0.017 ( 23 hom., cov: 32)
Exomes 𝑓: 0.023 ( 412 hom. )
Consequence
DNMBP
NM_015221.4 synonymous
NM_015221.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.350
Genes affected
DNMBP (HGNC:30373): (dynamin binding protein) This gene encodes a protein belonging to the guanine nucleotide exchange factor family, and which regulates the configuration of cell junctions. It contains multiple binding sites for dynamin and thus links dynamin to actin regulatory proteins. Polymorphisms in this gene have been linked to Alzheimer's disease in some populations, though there are conflicting reports of such linkages in other populations. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
Variant 10-99877160-C-T is Benign according to our data. Variant chr10-99877160-C-T is described in ClinVar as [Benign]. Clinvar id is 3038273.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=0.35 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0172 (2620/152240) while in subpopulation NFE AF= 0.0248 (1685/68020). AF 95% confidence interval is 0.0238. There are 23 homozygotes in gnomad4. There are 1258 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 23 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DNMBP | NM_015221.4 | c.4725G>A | p.Glu1575= | synonymous_variant | 17/17 | ENST00000324109.9 | NP_056036.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DNMBP | ENST00000324109.9 | c.4725G>A | p.Glu1575= | synonymous_variant | 17/17 | 1 | NM_015221.4 | ENSP00000315659 | P1 | |
DNMBP | ENST00000543621.6 | c.2589G>A | p.Glu863= | synonymous_variant | 14/14 | 1 | ENSP00000443657 | |||
DNMBP | ENST00000636706.1 | c.3621G>A | p.Glu1207= | synonymous_variant | 14/14 | 2 | ENSP00000489875 |
Frequencies
GnomAD3 genomes AF: 0.0172 AC: 2623AN: 152122Hom.: 23 Cov.: 32
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GnomAD3 exomes AF: 0.0185 AC: 4529AN: 245038Hom.: 68 AF XY: 0.0185 AC XY: 2447AN XY: 132466
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GnomAD4 exome AF: 0.0231 AC: 33664AN: 1457562Hom.: 412 Cov.: 31 AF XY: 0.0227 AC XY: 16446AN XY: 724952
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GnomAD4 genome AF: 0.0172 AC: 2620AN: 152240Hom.: 23 Cov.: 32 AF XY: 0.0169 AC XY: 1258AN XY: 74432
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
DNMBP-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 21, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at