Variant rs80178653 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001034853.2(RPGR):c.1059+25T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0339 in 1,157,980 control chromosomes in the GnomAD database, including 1,207 homozygotes. There are 13,490 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 92 hom., 1209 hem., cov: 22)

Exomes 𝑓: 0.034 ( 1115 hom. 12281 hem. )

Consequence

RPGR
NM_001034853.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.684

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant X-38301222-A-G is Benign according to our data. Variant chrX-38301222-A-G is described in ClinVar as [Benign]. Clinvar id is 257191.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.129 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.1059+25T>C		intron_variant		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.1059+25T>C		intron_variant			NM_001034853.2	ENSP00000495537.1		Q92834-6
ENSG00000250349	ENST00000465127.1 linkuse as main transcript	c.172-364899A>G		intron_variant		5		ENSP00000417050.1		B4E171

Frequencies

GnomAD3 genomes

AF:

0.0312

AC:

3480

AN:

111660

Hom.:

Cov.:

AF XY:

0.0356

AC XY:

1205

AN XY:

33834

show subpopulations

Gnomad AFR

AF:

0.00861

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0939

Gnomad ASJ

AF:

0.0257

Gnomad EAS

AF:

0.0723

Gnomad SAS

AF:

0.141

Gnomad FIN

AF:

0.0734

Gnomad MID

AF:

0.0169

Gnomad NFE

AF:

0.0196

Gnomad OTH

AF:

0.0353

GnomAD3 exomes

AF:

0.0712

AC:

11344

AN:

159227

Hom.:

672

AF XY:

0.0669

AC XY:

3258

AN XY:

48673

show subpopulations

Gnomad AFR exome

AF:

0.00854

Gnomad AMR exome

AF:

0.213

Gnomad ASJ exome

AF:

0.0189

Gnomad EAS exome

AF:

0.0701

Gnomad SAS exome

AF:

0.150

Gnomad FIN exome

AF:

0.0752

Gnomad NFE exome

AF:

0.0193

Gnomad OTH exome

AF:

0.0387

GnomAD4 exome

AF:

0.0342

AC:

35808

AN:

1046264

Hom.:

1115

Cov.:

AF XY:

0.0378

AC XY:

12281

AN XY:

324502

show subpopulations

Gnomad4 AFR exome

AF:

0.00837

Gnomad4 AMR exome

AF:

0.197

Gnomad4 ASJ exome

AF:

0.0190

Gnomad4 EAS exome

AF:

0.0784

Gnomad4 SAS exome

AF:

0.143

Gnomad4 FIN exome

AF:

0.0692

Gnomad4 NFE exome

AF:

0.0182

Gnomad4 OTH exome

AF:

0.0337

GnomAD4 genome

AF:

0.0312

AC:

3483

AN:

111716

Hom.:

Cov.:

AF XY:

0.0357

AC XY:

1209

AN XY:

33900

show subpopulations

Gnomad4 AFR

AF:

0.00859

Gnomad4 AMR

AF:

0.0941

Gnomad4 ASJ

AF:

0.0257

Gnomad4 EAS

AF:

0.0726

Gnomad4 SAS

AF:

0.141

Gnomad4 FIN

AF:

0.0734

Gnomad4 NFE

AF:

0.0196

Gnomad4 OTH

AF:

0.0348

Alfa

AF:

0.0235

Hom.:

184

Bravo

AF:

0.0350

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

7.8

DANN

Benign

0.88

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