rs5945176

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000631210.1(MECP2):​n.48-12651A>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 110,700 control chromosomes in the GnomAD database, including 5,583 homozygotes. There are 11,481 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 0.35 ( 5583 hom., 11481 hem., cov: 23)

Consequence

MECP2
ENST00000631210.1 intron, non_coding_transcript

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.233
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]

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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=-0.97).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MECP2ENST00000631210.1 linkuse as main transcriptn.48-12651A>C intron_variant, non_coding_transcript_variant 1

Frequencies

GnomAD3 genomes
AF:
0.353
AC:
39015
AN:
110644
Hom.:
5582
Cov.:
23
AF XY:
0.348
AC XY:
11455
AN XY:
32874
show subpopulations
Gnomad AFR
AF:
0.533
Gnomad AMI
AF:
0.0540
Gnomad AMR
AF:
0.243
Gnomad ASJ
AF:
0.337
Gnomad EAS
AF:
0.361
Gnomad SAS
AF:
0.515
Gnomad FIN
AF:
0.311
Gnomad MID
AF:
0.356
Gnomad NFE
AF:
0.272
Gnomad OTH
AF:
0.330
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.353
AC:
39035
AN:
110700
Hom.:
5583
Cov.:
23
AF XY:
0.349
AC XY:
11481
AN XY:
32940
show subpopulations
Gnomad4 AFR
AF:
0.532
Gnomad4 AMR
AF:
0.242
Gnomad4 ASJ
AF:
0.337
Gnomad4 EAS
AF:
0.361
Gnomad4 SAS
AF:
0.515
Gnomad4 FIN
AF:
0.311
Gnomad4 NFE
AF:
0.272
Gnomad4 OTH
AF:
0.337
Alfa
AF:
0.310
Hom.:
3067
Bravo
AF:
0.355

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.97
CADD
Benign
2.3
DANN
Benign
0.65

Splicing

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: rs5945176; hg19: chrX-153383163; API