X-67951456-G-T

Variant names:

• chrX-67951456-G-T
• rs2363785
• ENST00000680612.1:c.1687-1871C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000680612.1. 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPHN1	ENST00000680612.1		c.1687-1871C>A		intron	N/A	ENSP00000505365.1

Frequencies

GnomAD3 genomes AF: 0.436 AC: 47715 AN: 109477 Hom.: 8405 Cov.: 22

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

African (AFR) AF: 0.656 AC: 19724 AN: 30059

American (AMR) AF: 0.380 AC: 3889 AN: 10224

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 832 AN: 2620

East Asian (EAS) AF: 0.316 AC: 1076 AN: 3400

South Asian (SAS) AF: 0.330 AC: 849 AN: 2569

European-Finnish (FIN) AF: 0.321 AC: 1836 AN: 5718

Middle Eastern (MID) AF: 0.462 AC: 97 AN: 210

European-Non Finnish (NFE) AF: 0.355 AC: 18673 AN: 52572

Other (OTH) AF: 0.451 AC: 673 AN: 1493

Alfa AF: 0.353 Hom.: 9452

Bravo AF: 0.450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.45
DANN	Benign	0.37
PhyloP100		-0.070

Splicing

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

Other links and lift over

dbSNP: rs2363785; hg19: chrX-67171298;