chrX-68052289-CAA-C

Variant names:

• chrX-68052289-CAA-C
• rs72307579
• NM_002547.3:c.2375+249_2375+250delTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_002547.3(OPHN1):​c.2375+249_2375+250delTT 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 0.010 (4 hom., 82 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 = 0.0102 (627/61205) while in subpopulation AFR AF= 0.0322 (603/18746). AF 95% confidence interval is 0.03. There are 4 homozygotes in gnomad4. There are 82 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPHN1	NM_002547.3	c.2375+249_2375+250delTT		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+249_2375+250delTT		intron_variant	Intron 23 of 24	1	NM_002547.3	ENSP00000347710.5

Frequencies

GnomAD3 genomes AF: 0.0102 AC: 626 AN: 61228 Hom.: 4 Cov.: 0 AF XY: 0.0101 AC XY: 81 AN XY: 8000

Gnomad AFR AF: 0.0321

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00267

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00209

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000131

Gnomad OTH AF: 0.00513

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

GnomAD4 genome AF: 0.0102 AC: 627 AN: 61205 Hom.: 4 Cov.: 0 AF XY: 0.0103 AC XY: 82 AN XY: 7999

Gnomad4 AFR AF: 0.0322

Gnomad4 AMR AF: 0.00267

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00209

Gnomad4 NFE AF: 0.000131

Gnomad4 OTH AF: 0.00509

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;