X-68052289-C-CAA

Variant names:

• chrX-68052289-C-CAA
• rs72307579
• NM_002547.3:c.2375+249_2375+250dupTT

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+249_2375+250dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.058 (137 hom., 375 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-CAA is Benign according to our data. Variant chrX-68052289-C-CAA is described in ClinVar as Benign. ClinVar VariationId is 1260443.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0915 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+249_2375+250dupTT		intron	N/A	NP_002538.1	O60890-1
	OPHN1	NM_001437258.1		c.2051+249_2051+250dupTT		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+251insTT		intron	N/A	ENSP00000347710.5	O60890-1
	OPHN1	ENST00000905069.1		c.2375+250_2375+251insTT		intron	N/A	ENSP00000575128.1
	OPHN1	ENST00000681408.1		c.2270+250_2270+251insTT		intron	N/A	ENSP00000506619.1	A0A7P0TBH4

Frequencies

GnomAD3 genomes AF: 0.0579 AC: 3539 AN: 61106 Hom.: 137 Cov.: 0

Gnomad AFR AF: 0.0136

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.0243

Gnomad ASJ AF: 0.0485

Gnomad EAS AF: 0.000563

Gnomad SAS AF: 0.0636

Gnomad FIN AF: 0.0494

Gnomad MID AF: 0.0522

Gnomad NFE AF: 0.0944

Gnomad OTH AF: 0.0334

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

GnomAD4 genome AF: 0.0579 AC: 3537 AN: 61083 Hom.: 137 Cov.: 0 AF XY: 0.0470 AC XY: 375 AN XY: 7975

African (AFR) AF: 0.0136 AC: 254 AN: 18707

American (AMR) AF: 0.0242 AC: 118 AN: 4869

Ashkenazi Jewish (ASJ) AF: 0.0485 AC: 76 AN: 1568

East Asian (EAS) AF: 0.000567 AC: 1 AN: 1765

South Asian (SAS) AF: 0.0646 AC: 59 AN: 913

European-Finnish (FIN) AF: 0.0494 AC: 71 AN: 1438

Middle Eastern (MID) AF: 0.0500 AC: 5 AN: 100

European-Non Finnish (NFE) AF: 0.0944 AC: 2880 AN: 30520

Other (OTH) AF: 0.0331 AC: 26 AN: 786

Alfa AF: 0.0207 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

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

Other links and lift over

dbSNP: rs72307579; hg19: chrX-67272131;