X-68052289-C-CAA

Position:

• chrX-68052289-C-CAA

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+251insTT 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

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-CAA is Benign according to our data. Variant chrX-68052289-C-CAA is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0579 AC: 3539 AN: 61106 Hom.: 137 Cov.: 0 AF XY: 0.0470 AC XY: 375 AN XY: 7976

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

Gnomad4 AFR AF: 0.0136

Gnomad4 AMR AF: 0.0242

Gnomad4 ASJ AF: 0.0485

Gnomad4 EAS AF: 0.000567

Gnomad4 SAS AF: 0.0646

Gnomad4 FIN AF: 0.0494

Gnomad4 NFE AF: 0.0944

Gnomad4 OTH AF: 0.0331

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

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;