Variant X-68212097-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_002547.3(OPHN1):c.702+11A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00178 in 1,139,718 control chromosomes in the GnomAD database, including 3 homozygotes. There are 587 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., 33 hem., cov: 23)

Exomes 𝑓: 0.0019 ( 3 hom. 554 hem. )

Consequence

OPHN1
NM_002547.3 intron

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 0.0500

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant X-68212097-T-G is Benign according to our data. Variant chrX-68212097-T-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 159478.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1, Likely_benign=1}. Variant chrX-68212097-T-G is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 33 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPHN1	NM_002547.3 linkuse as main transcript	c.702+11A>C		intron_variant		ENST00000355520.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPHN1	ENST00000355520.6 linkuse as main transcript	c.702+11A>C		intron_variant		1	NM_002547.3	P1	O60890-1

Frequencies

GnomAD3 genomes

AF:

0.00117

AC:

131

AN:

111938

Hom.:

Cov.:

AF XY:

0.000967

AC XY:

AN XY:

34128

show subpopulations

Gnomad AFR

AF:

0.000422

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00218

Gnomad ASJ

AF:

0.00226

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000164

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00166

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00130

AC:

213

AN:

163335

Hom.:

AF XY:

0.00112

AC XY:

AN XY:

51569

show subpopulations

Gnomad AFR exome

AF:

0.000937

Gnomad AMR exome

AF:

0.00159

Gnomad ASJ exome

AF:

0.00183

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000243

Gnomad FIN exome

AF:

0.000136

Gnomad NFE exome

AF:

0.00191

Gnomad OTH exome

AF:

0.00170

GnomAD4 exome

AF:

0.00185

AC:

1902

AN:

1027780

Hom.:

Cov.:

AF XY:

0.00179

AC XY:

554

AN XY:

309376

show subpopulations

Gnomad4 AFR exome

AF:

0.000280

Gnomad4 AMR exome

AF:

0.00161

Gnomad4 ASJ exome

AF:

0.00192

Gnomad4 EAS exome

AF:

0.0000336

Gnomad4 SAS exome

AF:

0.000430

Gnomad4 FIN exome

AF:

0.000100

Gnomad4 NFE exome

AF:

0.00215

Gnomad4 OTH exome

AF:

0.00208

GnomAD4 genome

AF:

0.00117

AC:

131

AN:

111938

Hom.:

Cov.:

AF XY:

0.000967

AC XY:

AN XY:

34128

show subpopulations

Gnomad4 AFR

AF:

0.000422

Gnomad4 AMR

AF:

0.00218

Gnomad4 ASJ

AF:

0.00226

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000164

Gnomad4 NFE

AF:

0.00166

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00105

Hom.:

Bravo

AF:

0.00139

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

X-linked intellectual disability-cerebellar hypoplasia syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jun 12, 2013

- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 18, 2017

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 19, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.0

DANN

Benign

0.56

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over