ENST00000631210.1:n.48-5547G>A

Variant names:

• chrX-154110585-C-T
• rs5987211
• ENST00000631210.1:n.48-5547G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000631210.1(MECP2):​n.48-5547G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0891 in 111,814 control chromosomes in the GnomAD database, including 566 homozygotes. There are 2,679 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 0.089 (566 hom., 2679 hem., cov: 22)
• Consequence: MECP2 ENST00000631210.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.264
• Publications: 2 publications found

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]

MECP2 Gene-Disease associations (from GenCC):

• chromosome Xq28 duplication syndrome

  Inheritance: XL Classification: DEFINITIVE Submitted by: G2P
• Rett syndrome

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Orphanet, G2P
• severe neonatal-onset encephalopathy with microcephaly

  Inheritance: XL Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
• syndromic X-linked intellectual disability Lubs type

  Inheritance: XL Classification: DEFINITIVE Submitted by: G2P
• atypical Rett syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
• X-linked intellectual disability-psychosis-macroorchidism syndrome

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000631210.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MECP2	ENST00000631210.1	TSL:1	n.48-5547G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0889 AC: 9937 AN: 111762 Hom.: 563 Cov.: 22

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0489

Gnomad ASJ AF: 0.0393

Gnomad EAS AF: 0.0125

Gnomad SAS AF: 0.0294

Gnomad FIN AF: 0.0481

Gnomad MID AF: 0.0418

Gnomad NFE AF: 0.0515

Gnomad OTH AF: 0.0823

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0891 AC: 9965 AN: 111814 Hom.: 566 Cov.: 22 AF XY: 0.0787 AC XY: 2679 AN XY: 34032

African (AFR) AF: 0.197 AC: 6045 AN: 30663

American (AMR) AF: 0.0488 AC: 514 AN: 10531

Ashkenazi Jewish (ASJ) AF: 0.0393 AC: 104 AN: 2646

East Asian (EAS) AF: 0.0122 AC: 44 AN: 3604

South Asian (SAS) AF: 0.0295 AC: 80 AN: 2709

European-Finnish (FIN) AF: 0.0481 AC: 291 AN: 6055

Middle Eastern (MID) AF: 0.0459 AC: 10 AN: 218

European-Non Finnish (NFE) AF: 0.0515 AC: 2738 AN: 53180

Other (OTH) AF: 0.0911 AC: 139 AN: 1525

Alfa AF: 0.0772 Hom.: 458

Bravo AF: 0.0973

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.7
DANN	Benign	0.82
PhyloP100		0.26

Splicing

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

Other links and lift over

dbSNP: rs5987211; hg19: chrX-153376055;