rs1410127

Positions:

• chrX-68060539-C-T

Variant summary

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

The NM_002547.3(OPHN1):​c.2158+3315G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 111,261 control chromosomes in the GnomAD database, including 7,391 homozygotes. There are 13,074 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 (7391 hom., 13074 hem., cov: 23)
• Consequence: OPHN1 NM_002547.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPHN1	NM_002547.3	c.2158+3315G>A		intron_variant		ENST00000355520.6	NP_002538.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPHN1	ENST00000355520.6	c.2158+3315G>A		intron_variant		1	NM_002547.3	ENSP00000347710	P1

Frequencies

GnomAD3 genomes AF: 0.407 AC: 45216 AN: 111213 Hom.: 7381 Cov.: 23 AF XY: 0.390 AC XY: 13031 AN XY: 33439

Gnomad AFR AF: 0.619

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.407 AC: 45274 AN: 111261 Hom.: 7391 Cov.: 23 AF XY: 0.390 AC XY: 13074 AN XY: 33497

Gnomad4 AFR AF: 0.620

Gnomad4 AMR AF: 0.353

Gnomad4 ASJ AF: 0.321

Gnomad4 EAS AF: 0.290

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.405

Alfa AF: 0.347 Hom.: 4998

Bravo AF: 0.423

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.11
DANN	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs1410127; hg19: chrX-67280381;