X-68052289-C-CA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002547.3(OPHN1):c.2375+250_2375+251insT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.49 (7014 hom., 3376 hem., cov: 0)
• Consequence: OPHN1 NM_002547.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.11

Genes affected

OPHN1 (HGNC:8148): (oligophrenin 1) This gene encodes a Rho-GTPase-activating protein that promotes GTP hydrolysis of Rho subfamily members. Rho proteins are important mediators of intracellular signal transduction, which affects cell migration and cell morphogenesis. Mutations in this gene are responsible for OPHN1-related X-linked cognitive disability with cerebellar hypoplasia and distinctive facial dysmorhphism. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant X-68052289-C-CA is Benign according to our data. Variant chrX-68052289-C-CA is described in ClinVar as [Benign]. Clinvar id is 1243835.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPHN1	NM_002547.3	c.2375+250_2375+251insT		intron_variant		ENST00000355520.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPHN1	ENST00000355520.6	c.2375+250_2375+251insT		intron_variant		1	NM_002547.3	P1

Frequencies

GnomAD3 genomes AF: 0.489 AC: 29807 AN: 60916 Hom.: 7014 Cov.: 0 AF XY: 0.430 AC XY: 3375 AN XY: 7850

Gnomad AFR AF: 0.778

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.479

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

GnomAD4 genome AF: 0.489 AC: 29803 AN: 60895 Hom.: 7014 Cov.: 0 AF XY: 0.430 AC XY: 3376 AN XY: 7851

Gnomad4 AFR AF: 0.778

Gnomad4 AMR AF: 0.448

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.448

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.347

Gnomad4 OTH AF: 0.487

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs72307579; hg19: chrX-67272131;