rs3138341
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The NM_001276270.2(MBD4):c.1183+68T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00284 in 1,592,636 control chromosomes in the GnomAD database, including 86 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.013 ( 38 hom., cov: 32)
Exomes 𝑓: 0.0017 ( 48 hom. )
Consequence
MBD4
NM_001276270.2 intron
NM_001276270.2 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.0780
Genes affected
MBD4 (HGNC:6919): (methyl-CpG binding domain 4, DNA glycosylase) 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 an MBD domain at the N-terminus that functions both in binding to methylated DNA and in protein interactions and a C-terminal mismatch-specific glycosylase domain that is involved in DNA repair. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0133 (2028/152332) while in subpopulation AFR AF= 0.0437 (1818/41560). AF 95% confidence interval is 0.0421. There are 38 homozygotes in gnomad4. There are 962 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 38 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MBD4 | NM_001276270.2 | c.1183+68T>G | intron_variant | ENST00000429544.7 | NP_001263199.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MBD4 | ENST00000429544.7 | c.1183+68T>G | intron_variant | 1 | NM_001276270.2 | ENSP00000394080.2 |
Frequencies
GnomAD3 genomes AF: 0.0133 AC: 2017AN: 152214Hom.: 37 Cov.: 32
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GnomAD3 exomes AF: 0.00378 AC: 927AN: 245500Hom.: 17 AF XY: 0.00326 AC XY: 435AN XY: 133386
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GnomAD4 exome AF: 0.00173 AC: 2491AN: 1440304Hom.: 48 Cov.: 28 AF XY: 0.00157 AC XY: 1127AN XY: 716372
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GnomAD4 genome AF: 0.0133 AC: 2028AN: 152332Hom.: 38 Cov.: 32 AF XY: 0.0129 AC XY: 962AN XY: 74492
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ClinVar
Not reported inComputational 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