NM_002547.3:c.*8+241A>G

Variant names:

• chrX-68048175-T-C
• rs2768572
• NM_002547.3:c.*8+241A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002547.3(OPHN1):​c.*8+241A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 111,147 control chromosomes in the GnomAD database, including 2,969 homozygotes. There are 6,548 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.21 (2969 hom., 6548 hem., cov: 22)
• Consequence: OPHN1 NM_002547.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.53
• 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: ClinGen, G2P, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant X-68048175-T-C is Benign according to our data. Variant chrX-68048175-T-C is described in ClinVar as Benign. ClinVar VariationId is 1295364.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.463 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPHN1	NM_002547.3	MANE Select	c.*8+241A>G		intron	N/A	NP_002538.1	O60890-1
	OPHN1	NM_001437258.1		c.*8+241A>G		intron	N/A	NP_001424187.1	A0A7P0Z4E9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPHN1	ENST00000355520.6	TSL:1 MANE Select	c.*8+241A>G		intron	N/A	ENSP00000347710.5	O60890-1
	OPHN1	ENST00000905069.1		c.*8+241A>G		intron	N/A	ENSP00000575128.1
	OPHN1	ENST00000681408.1		c.*8+241A>G		intron	N/A	ENSP00000506619.1	A0A7P0TBH4

Frequencies

GnomAD3 genomes AF: 0.208 AC: 23071 AN: 111094 Hom.: 2959 Cov.: 22

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.0234

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.0756

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.0369

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0803

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.208 AC: 23121 AN: 111147 Hom.: 2969 Cov.: 22 AF XY: 0.196 AC XY: 6548 AN XY: 33409

African (AFR) AF: 0.469 AC: 14243 AN: 30338

American (AMR) AF: 0.209 AC: 2196 AN: 10487

Ashkenazi Jewish (ASJ) AF: 0.0756 AC: 199 AN: 2633

East Asian (EAS) AF: 0.285 AC: 994 AN: 3492

South Asian (SAS) AF: 0.236 AC: 618 AN: 2622

European-Finnish (FIN) AF: 0.0369 AC: 224 AN: 6072

Middle Eastern (MID) AF: 0.133 AC: 29 AN: 218

European-Non Finnish (NFE) AF: 0.0803 AC: 4261 AN: 53092

Other (OTH) AF: 0.226 AC: 341 AN: 1510

Alfa AF: 0.134 Hom.: 1337

Bravo AF: 0.239

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.12
DANN	Benign	0.32
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2768572; hg19: chrX-67268017;