rs492933

Variant names:

• chrX-68044002-C-T
• rs492933
• NM_002547.3:c.*3170G>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.*3170G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 111,088 control chromosomes in the GnomAD database, including 12,200 homozygotes. There are 15,508 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 0.49 (12200 hom., 15508 hem., cov: 23)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: OPHN1 NM_002547.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 7 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPHN1	NM_002547.3	c.*3170G>A		3_prime_UTR_variant	Exon 25 of 25	ENST00000355520.6	NP_002538.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPHN1	ENST00000355520.6	c.*3170G>A		3_prime_UTR_variant	Exon 25 of 25	1	NM_002547.3	ENSP00000347710.5
OPHN1	ENST00000679822.1	c.*3070G>A		3_prime_UTR_variant	Exon 20 of 20			ENSP00000505810.1
OPHN1	ENST00000680612.1	c.1686+52868G>A		intron_variant	Intron 19 of 19			ENSP00000505365.1

Frequencies

GnomAD3 genomes AF: 0.488 AC: 54235 AN: 111034 Hom.: 12185 Cov.: 23

Gnomad AFR AF: 0.892

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.390

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.476

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 3 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 3

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 3

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.489 AC: 54312 AN: 111088 Hom.: 12200 Cov.: 23 AF XY: 0.466 AC XY: 15508 AN XY: 33312

African (AFR) AF: 0.892 AC: 27178 AN: 30460

American (AMR) AF: 0.387 AC: 4047 AN: 10447

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 856 AN: 2639

East Asian (EAS) AF: 0.284 AC: 991 AN: 3491

South Asian (SAS) AF: 0.344 AC: 911 AN: 2651

European-Finnish (FIN) AF: 0.255 AC: 1527 AN: 5983

Middle Eastern (MID) AF: 0.409 AC: 88 AN: 215

European-Non Finnish (NFE) AF: 0.334 AC: 17721 AN: 53020

Other (OTH) AF: 0.482 AC: 726 AN: 1507

Alfa AF: 0.383 Hom.: 28688

Bravo AF: 0.515

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.53
DANN	Benign	0.37
PhyloP100		-1.2
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: rs492933; hg19: chrX-67263844;