X-68145273-T-C

Variant names:

• chrX-68145273-T-C
• rs7887862
• NM_002547.3:c.1277-25941A>G

Variant summary

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

The NM_002547.3(OPHN1):​c.1277-25941A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 111,031 control chromosomes in the GnomAD database, including 3,313 homozygotes. There are 7,159 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 0.23 (3313 hom., 7159 hem., cov: 22)
• Consequence: OPHN1 NM_002547.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPHN1	NM_002547.3	c.1277-25941A>G		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.1277-25941A>G		intron_variant	Intron 15 of 24	1	NM_002547.3	ENSP00000347710.5

Frequencies

GnomAD3 genomes AF: 0.231 AC: 25664 AN: 110982 Hom.: 3310 Cov.: 22

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.0915

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.0729

Gnomad MID AF: 0.122

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.232 AC: 25709 AN: 111031 Hom.: 3313 Cov.: 22 AF XY: 0.215 AC XY: 7159 AN XY: 33301

African (AFR) AF: 0.461 AC: 14030 AN: 30413

American (AMR) AF: 0.248 AC: 2595 AN: 10464

Ashkenazi Jewish (ASJ) AF: 0.0915 AC: 241 AN: 2635

East Asian (EAS) AF: 0.442 AC: 1535 AN: 3474

South Asian (SAS) AF: 0.182 AC: 482 AN: 2644

European-Finnish (FIN) AF: 0.0729 AC: 441 AN: 6046

Middle Eastern (MID) AF: 0.124 AC: 27 AN: 217

European-Non Finnish (NFE) AF: 0.111 AC: 5859 AN: 52952

Other (OTH) AF: 0.227 AC: 344 AN: 1513

Alfa AF: 0.209 Hom.: 2937

Bravo AF: 0.259

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	15
DANN	Benign	0.76
PhyloP100		1.7
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: rs7887862; hg19: chrX-67365115;