chrX-68145273-T-C

Position:

• chrX-68145273-T-C

Variant summary

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

The NM_002547.3(OPHN1):​c.1277-25941A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 111,031 control chromosomes in the GnomAD database, including 3,313 homozygotes. There are 7,159 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 0.23 (3313 hom., 7159 hem., cov: 22)
• Consequence: OPHN1 NM_002547.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPHN1	NM_002547.3	c.1277-25941A>G		intron_variant		ENST00000355520.6	NP_002538.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPHN1	ENST00000355520.6	c.1277-25941A>G		intron_variant		1	NM_002547.3	ENSP00000347710.5

Frequencies

GnomAD3 genomes AF: 0.231 AC: 25664 AN: 110982 Hom.: 3310 Cov.: 22 AF XY: 0.214 AC XY: 7125 AN XY: 33242

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.0915

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.0729

Gnomad MID AF: 0.122

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.232 AC: 25709 AN: 111031 Hom.: 3313 Cov.: 22 AF XY: 0.215 AC XY: 7159 AN XY: 33301

Gnomad4 AFR AF: 0.461

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.0915

Gnomad4 EAS AF: 0.442

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.0729

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.227

Alfa AF: 0.170 Hom.: 1019

Bravo AF: 0.259

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	15
DANN	Benign	0.76

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: rs7887862; hg19: chrX-67365115;