chrX-68052289-CA-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 -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 male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 13 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPHN1	NM_002547.3	c.2375+250delT		intron_variant	Intron 23 of 24	ENST00000355520.6	NP_002538.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPHN1	ENST00000355520.6	c.2375+250delT		intron_variant	Intron 23 of 24	1	NM_002547.3	ENSP00000347710.5

Frequencies

GnomAD3 genomes AF: 0.0142 AC: 872 AN: 61200 Hom.: 13 Cov.: 0 AF XY: 0.00689 AC XY: 55 AN XY: 7988

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

Gnomad4 AFR AF: 0.0414

Gnomad4 AMR AF: 0.00636

Gnomad4 ASJ AF: 0.000637

Gnomad4 EAS AF: 0.00113

Gnomad4 SAS AF: 0.00545

Gnomad4 FIN AF: 0.0112

Gnomad4 NFE AF: 0.000948

Gnomad4 OTH AF: 0.0153

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs72307579; hg19: chrX-67272131;