X-68021892-T-C

Position:

• chrX-68021892-T-C

Variant summary

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

The ENST00000680612.1(OPHN1):​c.1687-72307A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 110,593 control chromosomes in the GnomAD database, including 9,689 homozygotes. There are 14,026 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 0.45 (9689 hom., 14026 hem., cov: 22)
• Consequence: OPHN1 ENST00000680612.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPHN1	ENST00000680612.1	c.1687-72307A>G		intron_variant				ENSP00000505365

Frequencies

GnomAD3 genomes AF: 0.446 AC: 49347 AN: 110540 Hom.: 9679 Cov.: 22 AF XY: 0.425 AC XY: 13976 AN XY: 32858

Gnomad AFR AF: 0.770

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.453

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

GnomAD4 genome AF: 0.447 AC: 49410 AN: 110593 Hom.: 9689 Cov.: 22 AF XY: 0.426 AC XY: 14026 AN XY: 32921

Gnomad4 AFR AF: 0.770

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.283

Gnomad4 EAS AF: 0.300

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.459

Alfa AF: 0.368 Hom.: 4203

Bravo AF: 0.470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.39
DANN	Benign	0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2768578; hg19: chrX-67241734;