chrX-68297933-G-C

Variant names:

• chrX-68297933-G-C
• rs5965536
• NM_002547.3:c.250+1068C>G

Variant summary

Our verdict is Benign. The variant received -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
• 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: Orphanet, ClinGen, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPHN1	NM_002547.3	MANE Select	c.250+1068C>G		intron	N/A	NP_002538.1
	OPHN1	NM_001437258.1		c.250+1068C>G		intron	N/A	NP_001424187.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPHN1	ENST00000355520.6	TSL:1 MANE Select	c.250+1068C>G		intron	N/A	ENSP00000347710.5
	OPHN1	ENST00000681408.1		c.250+1068C>G		intron	N/A	ENSP00000506619.1
	OPHN1	ENST00000679748.1		c.250+1068C>G		intron	N/A	ENSP00000505800.1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 37383 AN: 110727 Hom.: 8073 Cov.: 23

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

African (AFR) AF: 0.812 AC: 24697 AN: 30419

American (AMR) AF: 0.226 AC: 2343 AN: 10353

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 393 AN: 2636

East Asian (EAS) AF: 0.127 AC: 452 AN: 3549

South Asian (SAS) AF: 0.222 AC: 590 AN: 2657

European-Finnish (FIN) AF: 0.187 AC: 1076 AN: 5759

Middle Eastern (MID) AF: 0.182 AC: 38 AN: 209

European-Non Finnish (NFE) AF: 0.138 AC: 7289 AN: 52981

Other (OTH) AF: 0.314 AC: 476 AN: 1517

Alfa AF: 0.252 Hom.: 1805

Bravo AF: 0.365

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.12
DANN	Benign	0.31
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5965536; hg19: chrX-67517775;