chr19-49818330-A-G
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_030973.4(MED25):c.-12A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00975 in 1,571,294 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.014 ( 24 hom., cov: 33)
Exomes 𝑓: 0.0092 ( 90 hom. )
Consequence
MED25
NM_030973.4 5_prime_UTR
NM_030973.4 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.118
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
Variant 19-49818330-A-G is Benign according to our data. Variant chr19-49818330-A-G is described in ClinVar as [Benign]. Clinvar id is 138201.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-49818330-A-G is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0144 (2198/152258) while in subpopulation AFR AF= 0.0287 (1191/41568). AF 95% confidence interval is 0.0273. There are 24 homozygotes in gnomad4. There are 983 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 24 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MED25 | NM_030973.4 | c.-12A>G | 5_prime_UTR_variant | 1/18 | ENST00000312865.10 | ||
MED25 | NM_001378355.1 | c.-12A>G | 5_prime_UTR_variant | 1/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MED25 | ENST00000312865.10 | c.-12A>G | 5_prime_UTR_variant | 1/18 | 1 | NM_030973.4 |
Frequencies
GnomAD3 genomes ? AF: 0.0144 AC: 2192AN: 152140Hom.: 24 Cov.: 33
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GnomAD3 exomes AF: 0.00714 AC: 1274AN: 178518Hom.: 11 AF XY: 0.00658 AC XY: 643AN XY: 97676
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GnomAD4 exome AF: 0.00924 AC: 13117AN: 1419036Hom.: 90 Cov.: 34 AF XY: 0.00894 AC XY: 6283AN XY: 702652
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Charcot-Marie-Tooth disease Benign:1
Benign, criteria provided, single submitter | clinical testing | Molecular Genetics Laboratory, London Health Sciences Centre | - | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 20, 2014 | 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. - |
Congenital cataract-microcephaly-nevus flammeus simplex-severe intellectual disability syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 20, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
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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