rs191864898

Positions:

• chrX-18425467-G-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The variant allele was found at a frequency of 0.00634 in 113,430 control chromosomes in the GnomAD database, including 7 homozygotes. There are 214 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0063 (7 hom., 213 hem., cov: 24)
  • Exomes 𝑓: 0.0075 (0 hom. 1 hem.)
• Consequence: Unknown
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.199

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant X-18425467-G-T is Benign according to our data. Variant chrX-18425467-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 158175.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.00634 AC: 718 AN: 113248 Hom.: 7 Cov.: 24 AF XY: 0.00602 AC XY: 213 AN XY: 35386

Gnomad AFR AF: 0.00131

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00600

Gnomad ASJ AF: 0.00789

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000355

Gnomad FIN AF: 0.00728

Gnomad MID AF: 0.00418

Gnomad NFE AF: 0.00997

Gnomad OTH AF: 0.00716

GnomAD4 exome AF: 0.00752 AC: 1 AN: 133 Hom.: 0 AF XY: 0.0133 AC XY: 1 AN XY: 75

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00870

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00634 AC: 718 AN: 113297 Hom.: 7 Cov.: 24 AF XY: 0.00601 AC XY: 213 AN XY: 35445

Gnomad4 AFR AF: 0.00131

Gnomad4 AMR AF: 0.00599

Gnomad4 ASJ AF: 0.00789

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000356

Gnomad4 FIN AF: 0.00728

Gnomad4 NFE AF: 0.00997

Gnomad4 OTH AF: 0.00707

Alfa AF: 0.0107 Hom.: 59

Bravo AF: 0.00619

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, no assertion criteria provided	curation	RettBASE	May 09, 2014	Benign variation, found in normal male controls -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 22, 2021	- -

CDKL5 disorder Benign:1

Benign, criteria provided, single submitter

curation

Centre for Population Genomics, CPG

Jun 28, 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 v3 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	-0.82
CADD	Benign	6.6
DANN	Benign	0.87

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs191864898; hg19: chrX-18443587;