X-68048175-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002547.3(OPHN1):c.*8+241A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 111,147 control chromosomes in the GnomAD database, including 2,969 homozygotes. There are 6,548 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.21 (2969 hom., 6548 hem., cov: 22)
• Consequence: OPHN1 NM_002547.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.53

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant X-68048175-T-C is Benign according to our data. Variant chrX-68048175-T-C is described in ClinVar as [Benign]. Clinvar id is 1295364.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPHN1	NM_002547.3	c.*8+241A>G		intron_variant		ENST00000355520.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPHN1	ENST00000355520.6	c.*8+241A>G		intron_variant		1	NM_002547.3	P1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 23071 AN: 111094 Hom.: 2959 Cov.: 22 AF XY: 0.195 AC XY: 6515 AN XY: 33346

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.0234

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.0756

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.0369

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0803

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.208 AC: 23121 AN: 111147 Hom.: 2969 Cov.: 22 AF XY: 0.196 AC XY: 6548 AN XY: 33409

Gnomad4 AFR AF: 0.469

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.0756

Gnomad4 EAS AF: 0.285

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.0369

Gnomad4 NFE AF: 0.0803

Gnomad4 OTH AF: 0.226

Alfa AF: 0.134 Hom.: 1337

Bravo AF: 0.239

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.12
Dann	Benign	0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2768572; hg19: chrX-67268017;