rs1927232

Variant names:

• chrX-68163049-C-T
• rs1927232
• NM_002547.3:c.1276+29870G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002547.3(OPHN1):​c.1276+29870G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 109,871 control chromosomes in the GnomAD database, including 5,544 homozygotes. There are 10,723 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.35 (5544 hom., 10723 hem., cov: 22)
• Consequence: OPHN1 NM_002547.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.266
• Publications: 1 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: Orphanet, ClinGen, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPHN1	NM_002547.3	c.1276+29870G>A		intron_variant	Intron 15 of 24	ENST00000355520.6	NP_002538.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPHN1	ENST00000355520.6	c.1276+29870G>A		intron_variant	Intron 15 of 24	1	NM_002547.3	ENSP00000347710.5

Frequencies

GnomAD3 genomes AF: 0.351 AC: 38516 AN: 109830 Hom.: 5535 Cov.: 22

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.366

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.369

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

GnomAD4 genome AF: 0.351 AC: 38559 AN: 109871 Hom.: 5544 Cov.: 22 AF XY: 0.331 AC XY: 10723 AN XY: 32353

African (AFR) AF: 0.522 AC: 15808 AN: 30282

American (AMR) AF: 0.292 AC: 3016 AN: 10317

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 847 AN: 2608

East Asian (EAS) AF: 0.123 AC: 434 AN: 3525

South Asian (SAS) AF: 0.192 AC: 503 AN: 2622

European-Finnish (FIN) AF: 0.184 AC: 1060 AN: 5765

Middle Eastern (MID) AF: 0.390 AC: 83 AN: 213

European-Non Finnish (NFE) AF: 0.303 AC: 15863 AN: 52362

Other (OTH) AF: 0.376 AC: 564 AN: 1501

Alfa AF: 0.320 Hom.: 2322

Bravo AF: 0.362

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.73
PhyloP100		0.27
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1927232; hg19: chrX-67382891;