chrX-68060539-C-T

Variant names:

• chrX-68060539-C-T
• rs1410127
• NM_002547.3:c.2158+3315G>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.2158+3315G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 111,261 control chromosomes in the GnomAD database, including 7,391 homozygotes. There are 13,074 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 0.41 (7391 hom., 13074 hem., cov: 23)
• Consequence: OPHN1 NM_002547.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 3 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002547.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPHN1	NM_002547.3	MANE Select	c.2158+3315G>A		intron	N/A	NP_002538.1
	OPHN1	NM_001437258.1		c.1835-6729G>A		intron	N/A	NP_001424187.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPHN1	ENST00000355520.6	TSL:1 MANE Select	c.2158+3315G>A		intron	N/A	ENSP00000347710.5
	OPHN1	ENST00000681408.1		c.2053+3315G>A		intron	N/A	ENSP00000506619.1
	OPHN1	ENST00000679748.1		c.1835-6729G>A		intron	N/A	ENSP00000505800.1

Frequencies

GnomAD3 genomes AF: 0.407 AC: 45216 AN: 111213 Hom.: 7381 Cov.: 23

Gnomad AFR AF: 0.619

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.407 AC: 45274 AN: 111261 Hom.: 7391 Cov.: 23 AF XY: 0.390 AC XY: 13074 AN XY: 33497

African (AFR) AF: 0.620 AC: 18916 AN: 30519

American (AMR) AF: 0.353 AC: 3715 AN: 10528

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 849 AN: 2645

East Asian (EAS) AF: 0.290 AC: 1019 AN: 3512

South Asian (SAS) AF: 0.272 AC: 721 AN: 2646

European-Finnish (FIN) AF: 0.259 AC: 1549 AN: 5989

Middle Eastern (MID) AF: 0.412 AC: 89 AN: 216

European-Non Finnish (NFE) AF: 0.331 AC: 17533 AN: 53011

Other (OTH) AF: 0.405 AC: 612 AN: 1512

Alfa AF: 0.357 Hom.: 11530

Bravo AF: 0.423

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.11
DANN	Benign	0.43
PhyloP100		-1.4
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: rs1410127; hg19: chrX-67280381;