X-68101899-G-T

Position:

• chrX-68101899-G-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002547.3(OPHN1):​c.1527-4870C>A 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 0.77 (23143 hom., 25797 hem., cov: 24)
  • Failed GnomAD Quality Control
• Consequence: OPHN1 NM_002547.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0690

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPHN1	NM_002547.3	c.1527-4870C>A		intron_variant		ENST00000355520.6	NP_002538.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPHN1	ENST00000355520.6	c.1527-4870C>A		intron_variant		1	NM_002547.3	ENSP00000347710.5

Frequencies

GnomAD3 genomes AF: 0.771 AC: 85539 AN: 110918 Hom.: 23149 Cov.: 24 AF XY: 0.777 AC XY: 25743 AN XY: 33118

Gnomad AFR AF: 0.801

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.710

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.895

Gnomad FIN AF: 0.771

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.728

Gnomad OTH AF: 0.762

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.771 AC: 85582 AN: 110970 Hom.: 23143 Cov.: 24 AF XY: 0.777 AC XY: 25797 AN XY: 33180

Gnomad4 AFR AF: 0.800

Gnomad4 AMR AF: 0.826

Gnomad4 ASJ AF: 0.710

Gnomad4 EAS AF: 0.996

Gnomad4 SAS AF: 0.894

Gnomad4 FIN AF: 0.771

Gnomad4 NFE AF: 0.728

Gnomad4 OTH AF: 0.765

Alfa AF: 0.758 Hom.: 6291

Bravo AF: 0.780

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.49

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: rs1157321; hg19: chrX-67321741;