chrX-68052289-C-CA

Variant names:

• chrX-68052289-C-CA
• rs72307579
• NM_002547.3:c.2375+250dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002547.3(OPHN1):​c.2375+250dupT 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
• Publications: 0 publications found

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]

OPHN1 Gene-Disease associations (from GenCC):

• X-linked intellectual disability-cerebellar hypoplasia syndrome

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, G2P, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002547.3. 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
	OPHN1	NM_002547.3	MANE Select	c.2375+250dupT		intron	N/A	NP_002538.1	O60890-1
	OPHN1	NM_001437258.1		c.2051+250dupT		intron	N/A	NP_001424187.1	A0A7P0Z4E9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPHN1	ENST00000355520.6	TSL:1 MANE Select	c.2375+250_2375+251insT		intron	N/A	ENSP00000347710.5	O60890-1
	OPHN1	ENST00000905069.1		c.2375+250_2375+251insT		intron	N/A	ENSP00000575128.1
	OPHN1	ENST00000681408.1		c.2270+250_2270+251insT		intron	N/A	ENSP00000506619.1	A0A7P0TBH4

Frequencies

GnomAD3 genomes AF: 0.489 AC: 29807 AN: 60916 Hom.: 7014 Cov.: 0

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

African (AFR) AF: 0.778 AC: 14499 AN: 18646

American (AMR) AF: 0.448 AC: 2177 AN: 4854

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 633 AN: 1563

East Asian (EAS) AF: 0.448 AC: 784 AN: 1750

South Asian (SAS) AF: 0.273 AC: 250 AN: 916

European-Finnish (FIN) AF: 0.211 AC: 303 AN: 1435

Middle Eastern (MID) AF: 0.550 AC: 55 AN: 100

European-Non Finnish (NFE) AF: 0.347 AC: 10551 AN: 30436

Other (OTH) AF: 0.487 AC: 380 AN: 780

Alfa AF: 0.0548 Hom.: 152

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs72307579; hg19: chrX-67272131;