chr18-50275376-G-A
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2
The ENST00000592060.5(MBD1):c.489C>T(p.Pro163=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000773 in 1,611,116 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00049 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00080 ( 3 hom. )
Consequence
MBD1
ENST00000592060.5 synonymous
ENST00000592060.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.41
Genes affected
MBD1 (HGNC:6916): (methyl-CpG binding domain protein 1) The protein encoded by this gene is a member of a family of nuclear proteins related by the presence of a methyl-CpG binding domain (MBD). These proteins are capable of binding specifically to methylated DNA, and some members can also repress transcription from methylated gene promoters. This protein contains multiple domains: MBD at the N-terminus that functions both in binding to methylated DNA and in protein interactions; several CXXC-type zinc finger domains that mediate binding to non-methylated CpG dinucleotides; transcriptional repression domain (TRD) at the C-terminus that is involved in transcription repression and in protein interactions. Numerous alternatively spliced transcript variants encoding different isoforms have been noted for this gene.[provided by RefSeq, Feb 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP6
Variant 18-50275376-G-A is Benign according to our data. Variant chr18-50275376-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3053644.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=2.41 with no splicing effect.
BS2
High Homozygotes in GnomAdExome4 at 3 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MBD1 | NM_015846.4 | c.793-131C>T | intron_variant | ENST00000269468.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MBD1 | ENST00000269468.10 | c.793-131C>T | intron_variant | 5 | NM_015846.4 |
Frequencies
GnomAD3 genomes AF: 0.000486 AC: 74AN: 152178Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000449 AC: 107AN: 238086Hom.: 1 AF XY: 0.000436 AC XY: 57AN XY: 130596
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GnomAD4 exome AF: 0.000803 AC: 1171AN: 1458820Hom.: 3 Cov.: 33 AF XY: 0.000751 AC XY: 545AN XY: 725680
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GnomAD4 genome AF: 0.000486 AC: 74AN: 152296Hom.: 0 Cov.: 33 AF XY: 0.000416 AC XY: 31AN XY: 74470
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
MBD1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 21, 2019 | This variant is classified as likely 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
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at