rs5945175
Variant names:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The NM_001110792.2(MECP2):c.62+4305A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0262 in 110,926 control chromosomes in the GnomAD database, including 60 homozygotes. There are 806 hemizygotes in GnomAD. 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 0.026 ( 60 hom., 806 hem., cov: 21)
Consequence
MECP2
NM_001110792.2 intron
NM_001110792.2 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.230
Genes affected
MECP2 (HGNC:6990): (methyl-CpG binding protein 2) DNA methylation is the major modification of eukaryotic genomes and plays an essential role in mammalian development. Human proteins MECP2, MBD1, MBD2, MBD3, and MBD4 comprise a family of nuclear proteins related by the presence in each of a methyl-CpG binding domain (MBD). Each of these proteins, with the exception of MBD3, is capable of binding specifically to methylated DNA. MECP2, MBD1 and MBD2 can also repress transcription from methylated gene promoters. In contrast to other MBD family members, MECP2 is X-linked and subject to X inactivation. MECP2 is dispensible in stem cells, but is essential for embryonic development. MECP2 gene mutations are the cause of most cases of Rett syndrome, a progressive neurologic developmental disorder and one of the most common causes of cognitive disability in females. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2015]
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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=-0.89).
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0262 (2911/110926) while in subpopulation SAS AF= 0.0413 (109/2638). AF 95% confidence interval is 0.0392. There are 60 homozygotes in gnomad4. There are 806 alleles in male gnomad4 subpopulation. Median coverage is 21. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 60 XL gene
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| MECP2 | NM_001110792.2 | c.62+4305A>G | intron_variant | Intron 1 of 2 | ENST00000453960.7 | NP_001104262.1 | ||
| MECP2 | NM_004992.4 | c.-98-992A>G | intron_variant | Intron 1 of 3 | ENST00000303391.11 | NP_004983.1 |
Ensembl
Frequencies
GnomAD3 genomes 0.0263 AC: 2912AN: 110872Hom.: 60 Cov.: 21 AF XY: 0.0244 AC XY: 806AN XY: 33080
GnomAD3 genomes
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GnomAD4 genome 0.0262 AC: 2911AN: 110926Hom.: 60 Cov.: 21 AF XY: 0.0243 AC XY: 806AN XY: 33144
GnomAD4 genome
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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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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at