rs574703435
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM2BP4_StrongBP6_Very_StrongBS1
The NM_030973.4(MED25):c.1374+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000141 in 1,611,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00083 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000069 ( 0 hom. )
Consequence
MED25
NM_030973.4 intron
NM_030973.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.65
Genes affected
MED25 (HGNC:28845): (mediator complex subunit 25) This gene encodes a component of the transcriptional coactivator complex termed the Mediator complex. This complex is required for transcription of most RNA polymerase II-dependent genes. The encoded protein plays a role in chromatin modification and in preinitiation complex assembly. Mutations in this gene are associated with Charcot-Marie-Tooth disease type 2B2. [provided by RefSeq, Apr 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
?
Variant 19-49832166-C-T is Benign according to our data. Variant chr19-49832166-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 543262.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 = 0.000834 (127/152294) while in subpopulation AFR AF= 0.00298 (124/41556). AF 95% confidence interval is 0.00256. There are 0 homozygotes in gnomad4. There are 51 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MED25 | NM_030973.4 | c.1374+9C>T | intron_variant | ENST00000312865.10 | |||
MED25 | NM_001378355.1 | c.1374+9C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MED25 | ENST00000312865.10 | c.1374+9C>T | intron_variant | 1 | NM_030973.4 |
Frequencies
GnomAD3 genomes ? AF: 0.000821 AC: 125AN: 152176Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000215 AC: 53AN: 246936Hom.: 0 AF XY: 0.000149 AC XY: 20AN XY: 134250
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GnomAD4 exome AF: 0.0000685 AC: 100AN: 1459344Hom.: 0 Cov.: 35 AF XY: 0.0000606 AC XY: 44AN XY: 725928
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GnomAD4 genome ? AF: 0.000834 AC: 127AN: 152294Hom.: 0 Cov.: 32 AF XY: 0.000685 AC XY: 51AN XY: 74468
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Charcot-Marie-Tooth disease Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Molecular Genetics Laboratory, London Health Sciences Centre | - | - - |
Charcot-Marie-Tooth disease type 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 29, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at