ENST00000680612.1:c.1687-72307A>G

Variant names:

• chrX-68021892-T-C
• rs2768578
• ENST00000680612.1:c.1687-72307A>G

Variant summary

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

The ENST00000680612.1(OPHN1):​c.1687-72307A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 110,593 control chromosomes in the GnomAD database, including 9,689 homozygotes. There are 14,026 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 0.45 (9689 hom., 14026 hem., cov: 22)
• Consequence: OPHN1 ENST00000680612.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 2 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 = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPHN1	ENST00000680612.1	c.1687-72307A>G		intron_variant	Intron 19 of 19			ENSP00000505365.1

Frequencies

GnomAD3 genomes AF: 0.446 AC: 49347 AN: 110540 Hom.: 9679 Cov.: 22

Gnomad AFR AF: 0.770

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.453

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

GnomAD4 genome AF: 0.447 AC: 49410 AN: 110593 Hom.: 9689 Cov.: 22 AF XY: 0.426 AC XY: 14026 AN XY: 32921

African (AFR) AF: 0.770 AC: 23319 AN: 30268

American (AMR) AF: 0.374 AC: 3905 AN: 10430

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 745 AN: 2635

East Asian (EAS) AF: 0.300 AC: 1043 AN: 3476

South Asian (SAS) AF: 0.341 AC: 886 AN: 2599

European-Finnish (FIN) AF: 0.255 AC: 1508 AN: 5907

Middle Eastern (MID) AF: 0.439 AC: 93 AN: 212

European-Non Finnish (NFE) AF: 0.323 AC: 17087 AN: 52879

Other (OTH) AF: 0.459 AC: 692 AN: 1507

Alfa AF: 0.350 Hom.: 7091

Bravo AF: 0.470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.39
DANN	Benign	0.76
PhyloP100		-1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2768578; hg19: chrX-67241734;