rs5965550

Positions:

• chrX-68335209-T-A
• chrX-68335209-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002547.3(OPHN1):​c.155-36113A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.33 (8037 hom., 9179 hem., cov: 20)
• Consequence: OPHN1 NM_002547.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.337

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPHN1	NM_002547.3	c.155-36113A>T		intron_variant		ENST00000355520.6	NP_002538.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPHN1	ENST00000355520.6	c.155-36113A>T		intron_variant		1	NM_002547.3	ENSP00000347710	P1

Frequencies

GnomAD3 genomes AF: 0.333 AC: 35704 AN: 107064 Hom.: 8025 Cov.: 20 AF XY: 0.307 AC XY: 9147 AN XY: 29760

Gnomad AFR AF: 0.810

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.198

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.334 AC: 35756 AN: 107082 Hom.: 8037 Cov.: 20 AF XY: 0.308 AC XY: 9179 AN XY: 29788

Gnomad4 AFR AF: 0.810

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.310

Alfa AF: 0.230 Hom.: 1566

Bravo AF: 0.365

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.0
DANN	Benign	0.43

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: rs5965550; hg19: chrX-67555051;