rs5987211

chrX-154110585-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000631210.1(MECP2):n.48-5547G>A 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 0.0891 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, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.264

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MECP2	ENST00000631210.1	n.48-5547G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0889 AC: 9937 AN: 111762 Hom.: 563 Cov.: 22 AF XY: 0.0785 AC XY: 2666 AN XY: 33970

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

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.0488

Gnomad4 ASJ AF: 0.0393

Gnomad4 EAS AF: 0.0122

Gnomad4 SAS AF: 0.0295

Gnomad4 FIN AF: 0.0481

Gnomad4 NFE AF: 0.0515

Gnomad4 OTH AF: 0.0911

Alfa AF: 0.0772 Hom.: 458

Bravo AF: 0.0973

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	6.7
Dann	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5987211; hg19: chrX-153376055;