rs786205015

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

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.282
Variant links:
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
MECP2NM_001110792.2 linkuse as main transcriptc.414-70C>G intron_variant ENST00000453960.7 NP_001104262.1
MECP2NM_004992.4 linkuse as main transcriptc.378-70C>G intron_variant ENST00000303391.11 NP_004983.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MECP2ENST00000303391.11 linkuse as main transcriptc.378-70C>G intron_variant 1 NM_004992.4 ENSP00000301948 P1P51608-1
MECP2ENST00000453960.7 linkuse as main transcriptc.414-70C>G intron_variant 1 NM_001110792.2 ENSP00000395535 P51608-2

Frequencies

GnomAD3 genomes
AF:
0.0000178
AC:
2
AN:
112064
Hom.:
0
Cov.:
23
AF XY:
0.0000292
AC XY:
1
AN XY:
34214
show subpopulations
Gnomad AFR
AF:
0.0000325
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000164
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000290
AC:
30
AN:
1036190
Hom.:
0
AF XY:
0.0000384
AC XY:
12
AN XY:
312344
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000857
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000334
Gnomad4 SAS exome
AF:
0.0000382
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000266
Gnomad4 OTH exome
AF:
0.0000680
GnomAD4 genome
AF:
0.0000178
AC:
2
AN:
112064
Hom.:
0
Cov.:
23
AF XY:
0.0000292
AC XY:
1
AN XY:
34214
show subpopulations
Gnomad4 AFR
AF:
0.0000325
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000164
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000227

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 providedcurationRettBASEDec 05, 2013- -
Rett syndrome Benign:1
Benign, criteria provided, single submittercurationCentre for Population Genomics, CPGMar 15, 2024This 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
7.4
DANN
Benign
0.59

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs782440655; hg19: chrX-153296971; API