rs5965536

Positions:

• chrX-68297933-G-C

Variant summary

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

The NM_002547.3(OPHN1):​c.250+1068C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 110,755 control chromosomes in the GnomAD database, including 8,085 homozygotes. There are 10,687 hemizygotes in GnomAD. 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 0.34 (8085 hom., 10687 hem., cov: 23)
• Consequence: OPHN1 NM_002547.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.541

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPHN1	NM_002547.3	c.250+1068C>G		intron_variant		ENST00000355520.6	NP_002538.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPHN1	ENST00000355520.6	c.250+1068C>G		intron_variant		1	NM_002547.3	ENSP00000347710	P1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 37383 AN: 110727 Hom.: 8073 Cov.: 23 AF XY: 0.322 AC XY: 10646 AN XY: 33011

Gnomad AFR AF: 0.812

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.338 AC: 37444 AN: 110755 Hom.: 8085 Cov.: 23 AF XY: 0.323 AC XY: 10687 AN XY: 33049

Gnomad4 AFR AF: 0.812

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.314

Alfa AF: 0.252 Hom.: 1805

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	0.12
DANN	Benign	0.31

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: rs5965536; hg19: chrX-67517775;