Variant rs201730068 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PM4_SupportingBP6_Very_StrongBS1BS2

The NM_001034853.2(RPGR):c.2334_2336delGGA(p.Glu779del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00192 in 1,123,100 control chromosomes in the GnomAD database, including 35 homozygotes. There are 446 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 16 hom., 82 hem., cov: 12)

Exomes 𝑓: 0.0013 ( 19 hom. 364 hem. )

Consequence

RPGR
NM_001034853.2 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.518

Variant links:

Genes affected

RPGR (HGNC:10295): (retinitis pigmentosa GTPase regulator) This gene encodes a protein with a series of six RCC1-like domains (RLDs), characteristic of the highly conserved guanine nucleotide exchange factors. The encoded protein is found in the Golgi body and interacts with RPGRIP1. This protein localizes to the outer segment of rod photoreceptors and is essential for their viability. Mutations in this gene have been associated with X-linked retinitis pigmentosa (XLRP). Multiple alternatively spliced transcript variants that encode different isoforms of this gene have been reported, but the full-length natures of only some have been determined. [provided by RefSeq, Dec 2008]

RPGR links:

ENSG00000250349 (HGNC:):

ENSG00000250349 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001034853.2. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant X-38286662-TTCC-T is Benign according to our data. Variant chrX-38286662-TTCC-T is described in ClinVar as [Likely_benign]. Clinvar id is 446048.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.01 (777/77436) while in subpopulation AFR AF= 0.0353 (696/19714). AF 95% confidence interval is 0.0331. There are 16 homozygotes in gnomad4. There are 82 alleles in male gnomad4 subpopulation. Median coverage is 12. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 16 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPGR	NM_001034853.2 linkuse as main transcript	c.2334_2336delGGA	p.Glu779del	disruptive_inframe_deletion	15/15	ENST00000645032.1	NP_001030025.1	Q92834-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPGR	ENST00000645032.1 linkuse as main transcript	c.2334_2336delGGA	p.Glu779del	disruptive_inframe_deletion	15/15		NM_001034853.2	ENSP00000495537.1		Q92834-6
ENSG00000250349	ENST00000465127.1 linkuse as main transcript	c.172-379454_172-379452delCCT		intron_variant		5		ENSP00000417050.1		B4E171

Frequencies

GnomAD3 genomes

AF:

0.0100

AC:

777

AN:

77394

Hom.:

Cov.:

AF XY:

0.00690

AC XY:

AN XY:

11880

show subpopulations

Gnomad AFR

AF:

0.0354

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00948

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000124

Gnomad OTH

AF:

0.0117

GnomAD3 exomes

AF:

0.00398

AC:

451

AN:

113351

Hom.:

AF XY:

0.00271

AC XY:

109

AN XY:

40281

show subpopulations

Gnomad AFR exome

AF:

0.0464

Gnomad AMR exome

AF:

0.00512

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000211

Gnomad FIN exome

AF:

0.0000850

Gnomad NFE exome

AF:

0.0000470

Gnomad OTH exome

AF:

0.00275

GnomAD4 exome

AF:

0.00132

AC:

1379

AN:

1045664

Hom.:

AF XY:

0.00107

AC XY:

364

AN XY:

339624

show subpopulations

Gnomad4 AFR exome

AF:

0.0406

Gnomad4 AMR exome

AF:

0.00575

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000242

Gnomad4 FIN exome

AF:

0.0000537

Gnomad4 NFE exome

AF:

0.0000601

Gnomad4 OTH exome

AF:

0.00356

GnomAD4 genome

AF:

0.0100

AC:

777

AN:

77436

Hom.:

Cov.:

AF XY:

0.00688

AC XY:

AN XY:

11918

show subpopulations

Gnomad4 AFR

AF:

0.0353

Gnomad4 AMR

AF:

0.00946

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000124

Gnomad4 OTH

AF:

0.0115

Alfa

AF:

0.00652

Hom.:

Asia WGS

AF:

0.00159

AC:

AN:

2521

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	Jun 06, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Aug 28, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 14, 2018	- -

Primary ciliary dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 26, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over