Variant rs3788859 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002547.3(OPHN1):c.702+29G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,035,682 control chromosomes in the GnomAD database, including 4,372 homozygotes. There are 32,959 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 617 hom., 3892 hem., cov: 23)

Exomes 𝑓: 0.10 ( 3755 hom. 29067 hem. )

Consequence

OPHN1
NM_002547.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.847

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant X-68212079-C-T is Benign according to our data. Variant chrX-68212079-C-T is described in ClinVar as [Benign]. Clinvar id is 159479.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPHN1	NM_002547.3 link	c.702+29G>A		intron_variant		ENST00000355520.6	NP_002538.1	O60890-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPHN1	ENST00000355520.6 link	c.702+29G>A		intron_variant		1	NM_002547.3	ENSP00000347710.5		O60890-1

Frequencies

GnomAD3 genomes

AF:

0.119

AC:

13253

AN:

111072

Hom.:

610

Cov.:

AF XY:

0.116

AC XY:

3882

AN XY:

33330

show subpopulations

Gnomad AFR

AF:

0.152

Gnomad AMI

AF:

0.0830

Gnomad AMR

AF:

0.149

Gnomad ASJ

AF:

0.136

Gnomad EAS

AF:

0.128

Gnomad SAS

AF:

0.204

Gnomad FIN

AF:

0.0953

Gnomad MID

AF:

0.131

Gnomad NFE

AF:

0.0915

Gnomad OTH

AF:

0.134

GnomAD3 exomes

AF:

0.132

AC:

19548

AN:

148455

Hom.:

1009

AF XY:

0.134

AC XY:

6003

AN XY:

44905

show subpopulations

Gnomad AFR exome

AF:

0.155

Gnomad AMR exome

AF:

0.199

Gnomad ASJ exome

AF:

0.145

Gnomad EAS exome

AF:

0.132

Gnomad SAS exome

AF:

0.199

Gnomad FIN exome

AF:

0.0919

Gnomad NFE exome

AF:

0.0921

Gnomad OTH exome

AF:

0.133

GnomAD4 exome

AF:

0.103

AC:

95461

AN:

924557

Hom.:

3755

Cov.:

AF XY:

0.112

AC XY:

29067

AN XY:

259273

show subpopulations

Gnomad4 AFR exome

AF:

0.152

Gnomad4 AMR exome

AF:

0.195

Gnomad4 ASJ exome

AF:

0.142

Gnomad4 EAS exome

AF:

0.112

Gnomad4 SAS exome

AF:

0.195

Gnomad4 FIN exome

AF:

0.0905

Gnomad4 NFE exome

AF:

0.0892

Gnomad4 OTH exome

AF:

0.120

GnomAD4 genome

AF:

0.119

AC:

13276

AN:

111125

Hom.:

617

Cov.:

AF XY:

0.117

AC XY:

3892

AN XY:

33393

show subpopulations

Gnomad4 AFR

AF:

0.152

Gnomad4 AMR

AF:

0.150

Gnomad4 ASJ

AF:

0.136

Gnomad4 EAS

AF:

0.128

Gnomad4 SAS

AF:

0.204

Gnomad4 FIN

AF:

0.0953

Gnomad4 NFE

AF:

0.0915

Gnomad4 OTH

AF:

0.143

Alfa

AF:

0.104

Hom.:

4039

Bravo

AF:

0.128

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.86

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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