NM_002547.3:c.2375+248delT

Variant names:

• chrX-68052289-CA-C
• rs72307579
• NM_002547.3:c.2375+250delT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_002547.3(OPHN1):​c.2375+250delT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.014 (13 hom., 54 hem., cov: 0)
• Consequence: OPHN1 NM_002547.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.11
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• X-linked intellectual disability-cerebellar hypoplasia syndrome

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, G2P, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0143 (872/61177) while in subpopulation AFR AF = 0.0414 (776/18722). AF 95% confidence interval is 0.039. There are 13 homozygotes in GnomAd4. There are 54 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002547.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPHN1	NM_002547.3	MANE Select	c.2375+250delT		intron	N/A	NP_002538.1	O60890-1
	OPHN1	NM_001437258.1		c.2051+250delT		intron	N/A	NP_001424187.1	A0A7P0Z4E9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPHN1	ENST00000355520.6	TSL:1 MANE Select	c.2375+250delT		intron	N/A	ENSP00000347710.5	O60890-1
	OPHN1	ENST00000905069.1		c.2375+250delT		intron	N/A	ENSP00000575128.1
	OPHN1	ENST00000681408.1		c.2270+250delT		intron	N/A	ENSP00000506619.1	A0A7P0TBH4

Frequencies

GnomAD3 genomes AF: 0.0142 AC: 872 AN: 61200 Hom.: 13 Cov.: 0

Gnomad AFR AF: 0.0414

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00637

Gnomad ASJ AF: 0.000637

Gnomad EAS AF: 0.00113

Gnomad SAS AF: 0.00644

Gnomad FIN AF: 0.0112

Gnomad MID AF: 0.00870

Gnomad NFE AF: 0.000948

Gnomad OTH AF: 0.0154

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

GnomAD4 genome AF: 0.0143 AC: 872 AN: 61177 Hom.: 13 Cov.: 0 AF XY: 0.00676 AC XY: 54 AN XY: 7987

African (AFR) AF: 0.0414 AC: 776 AN: 18722

American (AMR) AF: 0.00636 AC: 31 AN: 4876

Ashkenazi Jewish (ASJ) AF: 0.000637 AC: 1 AN: 1571

East Asian (EAS) AF: 0.00113 AC: 2 AN: 1763

South Asian (SAS) AF: 0.00545 AC: 5 AN: 918

European-Finnish (FIN) AF: 0.0112 AC: 16 AN: 1433

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 100

European-Non Finnish (NFE) AF: 0.000948 AC: 29 AN: 30590

Other (OTH) AF: 0.0153 AC: 12 AN: 786

Alfa AF: 0.00 Hom.: 152

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1
Mutation Taster		=100/0	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs72307579; hg19: chrX-67272131;