rs1936313

chrX-67980806-T-CchrX-67980806-T-G

Variant summary

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

The ENST00000680612.1(OPHN1):c.1687-31221A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 110,075 control chromosomes in the GnomAD database, including 7,056 homozygotes. There are 12,746 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 0.41 (7056 hom., 12746 hem., cov: 22)
• Consequence: OPHN1 ENST00000680612.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.715

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPHN1	ENST00000680612.1	c.1687-31221A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.408 AC: 44842 AN: 110024 Hom.: 7049 Cov.: 22 AF XY: 0.394 AC XY: 12720 AN XY: 32300

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.428

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.414

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

GnomAD4 genome AF: 0.408 AC: 44876 AN: 110075 Hom.: 7056 Cov.: 22 AF XY: 0.394 AC XY: 12746 AN XY: 32361

Gnomad4 AFR AF: 0.558

Gnomad4 AMR AF: 0.367

Gnomad4 ASJ AF: 0.314

Gnomad4 EAS AF: 0.276

Gnomad4 SAS AF: 0.355

Gnomad4 FIN AF: 0.325

Gnomad4 NFE AF: 0.357

Gnomad4 OTH AF: 0.420

Alfa AF: 0.290 Hom.: 2032

Bravo AF: 0.418

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	8.4
Dann	Benign	0.84

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1936313; hg19: chrX-67200648;