rs786205015
Positions:
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The ENST00000453960.7(MECP2):c.414-70C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,148,254 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 13 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 23)
Exomes 𝑓: 0.000029 ( 0 hom. 12 hem. )
Consequence
MECP2
ENST00000453960.7 intron
ENST00000453960.7 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.282
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant X-154031520-G-C is Benign according to our data. Variant chrX-154031520-G-C is described in ClinVar as [Benign]. Clinvar id is 189626.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-154031520-G-C is described in Lovd as [Benign].
BS2
High Hemizygotes in GnomAdExome4 at 12 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MECP2 | NM_001110792.2 | c.414-70C>G | intron_variant | ENST00000453960.7 | NP_001104262.1 | |||
MECP2 | NM_004992.4 | c.378-70C>G | intron_variant | ENST00000303391.11 | NP_004983.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MECP2 | ENST00000303391.11 | c.378-70C>G | intron_variant | 1 | NM_004992.4 | ENSP00000301948 | P1 | |||
MECP2 | ENST00000453960.7 | c.414-70C>G | intron_variant | 1 | NM_001110792.2 | ENSP00000395535 |
Frequencies
GnomAD3 genomes AF: 0.0000178 AC: 2AN: 112064Hom.: 0 Cov.: 23 AF XY: 0.0000292 AC XY: 1AN XY: 34214
GnomAD3 genomes
AF:
AC:
2
AN:
112064
Hom.:
Cov.:
23
AF XY:
AC XY:
1
AN XY:
34214
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.0000290 AC: 30AN: 1036190Hom.: 0 AF XY: 0.0000384 AC XY: 12AN XY: 312344
GnomAD4 exome
AF:
AC:
30
AN:
1036190
Hom.:
AF XY:
AC XY:
12
AN XY:
312344
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000178 AC: 2AN: 112064Hom.: 0 Cov.: 23 AF XY: 0.0000292 AC XY: 1AN XY: 34214
GnomAD4 genome
AF:
AC:
2
AN:
112064
Hom.:
Cov.:
23
AF XY:
AC XY:
1
AN XY:
34214
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, no assertion criteria provided | curation | RettBASE | Dec 05, 2013 | - - |
Rett syndrome Benign:1
Benign, criteria provided, single submitter | curation | Centre for Population Genomics, CPG | Mar 15, 2024 | This variant has been collected from RettBASE and curated to current modified ACMG/AMP criteria. Based on the classification scheme defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like Disorders Specifications to the ACMG/AMP Variant Interpretation Guidelines VCEP 3.0, this variant is classified as benign. At least the following criteria are met: The allele frequency of this variant in at least one population in gnomAD is higher than the 0.03% threshold defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like Disorders VCEP 3.0 (BA1). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at