X-67951456-G-T

Position:

• chrX-67951456-G-T

Variant summary

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

The ENST00000680612.1(OPHN1):​c.1687-1871C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 109,532 control chromosomes in the GnomAD database, including 8,418 homozygotes. There are 13,390 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 0.44 (8418 hom., 13390 hem., cov: 22)
• Consequence: OPHN1 ENST00000680612.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.67951456G>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPHN1	ENST00000680612.1	c.1687-1871C>A		intron_variant				ENSP00000505365.1

Frequencies

GnomAD3 genomes AF: 0.436 AC: 47715 AN: 109477 Hom.: 8405 Cov.: 22 AF XY: 0.420 AC XY: 13347 AN XY: 31757

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.442

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.444

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

GnomAD4 genome AF: 0.436 AC: 47773 AN: 109532 Hom.: 8418 Cov.: 22 AF XY: 0.421 AC XY: 13390 AN XY: 31822

Gnomad4 AFR AF: 0.656

Gnomad4 AMR AF: 0.380

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.316

Gnomad4 SAS AF: 0.330

Gnomad4 FIN AF: 0.321

Gnomad4 NFE AF: 0.355

Gnomad4 OTH AF: 0.451

Alfa AF: 0.297 Hom.: 2402

Bravo AF: 0.450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.45
DANN	Benign	0.37

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2363785; hg19: chrX-67171298;