Variant X-68048476-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002547.3(OPHN1):c.2376-19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000968 in 1,197,902 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 26 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00048 ( 0 hom., 11 hem., cov: 23)

Exomes 𝑓: 0.000057 ( 0 hom. 15 hem. )

Consequence

OPHN1
NM_002547.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.57

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant X-68048476-G-A is Benign according to our data. Variant chrX-68048476-G-A is described in ClinVar as [Benign]. Clinvar id is 2043076.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 11 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPHN1	NM_002547.3 linkuse as main transcript	c.2376-19C>T		intron_variant		ENST00000355520.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPHN1	ENST00000355520.6 linkuse as main transcript	c.2376-19C>T		intron_variant		1	NM_002547.3	P1	O60890-1

Frequencies

GnomAD3 genomes

AF:

0.000482

AC:

AN:

111999

Hom.:

Cov.:

AF XY:

0.000322

AC XY:

AN XY:

34169

show subpopulations

Gnomad AFR

AF:

0.00166

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000948

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.000664

GnomAD3 exomes

AF:

0.000188

AC:

AN:

180571

Hom.:

AF XY:

0.0000612

AC XY:

AN XY:

65373

show subpopulations

Gnomad AFR exome

AF:

0.00222

Gnomad AMR exome

AF:

0.0000367

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000162

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000124

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000571

AC:

AN:

1085848

Hom.:

Cov.:

AF XY:

0.0000426

AC XY:

AN XY:

351786

show subpopulations

Gnomad4 AFR exome

AF:

0.00176

Gnomad4 AMR exome

AF:

0.0000285

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000746

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.0000438

GnomAD4 genome

AF:

0.000482

AC:

AN:

112054

Hom.:

Cov.:

AF XY:

0.000321

AC XY:

AN XY:

34234

show subpopulations

Gnomad4 AFR

AF:

0.00165

Gnomad4 AMR

AF:

0.0000947

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.000656

Alfa

AF:

0.000498

Hom.:

Bravo

AF:

0.000499

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 21, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.74

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