Variant rs199896738 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4BP6_Very_StrongBA1

The NM_001034853.2(RPGR):c.3060_3071del(p.Val1025_Glu1028del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.074 in 1,110,662 control chromosomes in the GnomAD database, including 2,635 homozygotes. There are 24,066 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.047 ( 119 hom., 339 hem., cov: 0)

Exomes 𝑓: 0.076 ( 2516 hom. 23727 hem. )

Consequence

RPGR
NM_001034853.2 inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.627

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001034853.2.

BP6

Variant X-38285927-CTCCCCTTCCACT-C is Benign according to our data. Variant chrX-38285927-CTCCCCTTCCACT-C is described in ClinVar as [Benign]. Clinvar id is 403391.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-38285927-CTCCCCTTCCACT-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPGR	NM_001034853.2 linkuse as main transcript	c.3060_3071del	p.Val1025_Glu1028del	inframe_deletion	15/15	ENST00000645032.1	NP_001030025.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPGR	ENST00000645032.1 linkuse as main transcript	c.3060_3071del	p.Val1025_Glu1028del	inframe_deletion	15/15		NM_001034853.2	ENSP00000495537	A2	Q92834-6

Frequencies

GnomAD3 genomes

AF:

0.0474

AC:

4077

AN:

85926

Hom.:

119

Cov.:

AF XY:

0.0200

AC XY:

339

AN XY:

16974

show subpopulations

Gnomad AFR

AF:

0.0160

Gnomad AMI

AF:

0.0139

Gnomad AMR

AF:

0.0299

Gnomad ASJ

AF:

0.0608

Gnomad EAS

AF:

0.000371

Gnomad SAS

AF:

0.0199

Gnomad FIN

AF:

0.0300

Gnomad MID

AF:

0.0335

Gnomad NFE

AF:

0.0734

Gnomad OTH

AF:

0.0446

GnomAD3 exomes

AF:

0.0524

AC:

6503

AN:

123985

Hom.:

184

AF XY:

0.0500

AC XY:

1870

AN XY:

37383

show subpopulations

Gnomad AFR exome

AF:

0.0193

Gnomad AMR exome

AF:

0.0341

Gnomad ASJ exome

AF:

0.0643

Gnomad EAS exome

AF:

0.000404

Gnomad SAS exome

AF:

0.0271

Gnomad FIN exome

AF:

0.0581

Gnomad NFE exome

AF:

0.0813

Gnomad OTH exome

AF:

0.0582

GnomAD4 exome

AF:

0.0763

AC:

78159

AN:

1024694

Hom.:

2516

AF XY:

0.0723

AC XY:

23727

AN XY:

328400

show subpopulations

Gnomad4 AFR exome

AF:

0.0202

Gnomad4 AMR exome

AF:

0.0368

Gnomad4 ASJ exome

AF:

0.0681

Gnomad4 EAS exome

AF:

0.000248

Gnomad4 SAS exome

AF:

0.0298

Gnomad4 FIN exome

AF:

0.0708

Gnomad4 NFE exome

AF:

0.0858

Gnomad4 OTH exome

AF:

0.0718

GnomAD4 genome

AF:

0.0474

AC:

4076

AN:

85968

Hom.:

119

Cov.:

AF XY:

0.0199

AC XY:

339

AN XY:

17014

show subpopulations

Gnomad4 AFR

AF:

0.0159

Gnomad4 AMR

AF:

0.0298

Gnomad4 ASJ

AF:

0.0608

Gnomad4 EAS

AF:

0.000372

Gnomad4 SAS

AF:

0.0199

Gnomad4 FIN

AF:

0.0300

Gnomad4 NFE

AF:

0.0734

Gnomad4 OTH

AF:

0.0439

Alfa

AF:

0.0642

Hom.:

444

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Primary ciliary dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 03, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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