ENST00000465127.1:c.172-391078G>A

Variant names:

Variant summary

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

The ENST00000465127.1(ENSG00000250349):c.172-391078G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0486 in 963,272 control chromosomes in the GnomAD database, including 1,001 homozygotes. There are 12,345 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.036 ( 87 hom., 1032 hem., cov: 22)

Exomes 𝑓: 0.050 ( 914 hom. 11313 hem. )

Consequence

ENSG00000250349
ENST00000465127.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.39

Variant links:

Genes affected

ENSG00000250349 (HGNC:):

ENSG00000250349 links:

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant X-38275043-G-A is Benign according to our data. Variant chrX-38275043-G-A is described in ClinVar as [Benign]. Clinvar id is 255834.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-38275043-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.057 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
RPGR	NM_000328.3 link	c.2149+46C>T	intron_variant	Intron 17 of 18	NP_000319.1	Q92834-2
RPGR	NM_001367245.1 link	c.2146+46C>T	intron_variant	Intron 17 of 18	NP_001354174.1
RPGR	NM_001367246.1 link	c.1963+46C>T	intron_variant	Intron 16 of 17	NP_001354175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000250349	ENST00000465127.1 link	c.172-391078G>A		intron_variant	Intron 3 of 8	5		ENSP00000417050.1		B4E171

Frequencies

GnomAD3 genomes

AF:

0.0362

AC:

4014

AN:

110956

Hom.:

Cov.:

AF XY:

0.0310

AC XY:

1031

AN XY:

33222

show subpopulations

Gnomad AFR

AF:

0.00750

Gnomad AMI

AF:

0.0562

Gnomad AMR

AF:

0.0225

Gnomad ASJ

AF:

0.0353

Gnomad EAS

AF:

0.000280

Gnomad SAS

AF:

0.0133

Gnomad FIN

AF:

0.0378

Gnomad MID

AF:

0.0170

Gnomad NFE

AF:

0.0587

Gnomad OTH

AF:

0.0370

GnomAD3 exomes

AF:

0.0372

AC:

6371

AN:

171074

Hom.:

106

AF XY:

0.0356

AC XY:

2065

AN XY:

58036

show subpopulations

Gnomad AFR exome

AF:

0.00632

Gnomad AMR exome

AF:

0.0156

Gnomad ASJ exome

AF:

0.0446

Gnomad EAS exome

AF:

0.0000753

Gnomad SAS exome

AF:

0.0219

Gnomad FIN exome

AF:

0.0424

Gnomad NFE exome

AF:

0.0585

Gnomad OTH exome

AF:

0.0358

GnomAD4 exome

AF:

0.0502

AC:

42765

AN:

852268

Hom.:

914

Cov.:

AF XY:

0.0474

AC XY:

11313

AN XY:

238542

show subpopulations

Gnomad4 AFR exome

AF:

0.00613

Gnomad4 AMR exome

AF:

0.0158

Gnomad4 ASJ exome

AF:

0.0432

Gnomad4 EAS exome

AF:

0.0000690

Gnomad4 SAS exome

AF:

0.0233

Gnomad4 FIN exome

AF:

0.0455

Gnomad4 NFE exome

AF:

0.0594

Gnomad4 OTH exome

AF:

0.0414

GnomAD4 genome

AF:

0.0362

AC:

4016

AN:

111004

Hom.:

Cov.:

AF XY:

0.0310

AC XY:

1032

AN XY:

33280

show subpopulations

Gnomad4 AFR

AF:

0.00748

Gnomad4 AMR

AF:

0.0225

Gnomad4 ASJ

AF:

0.0353

Gnomad4 EAS

AF:

0.000281

Gnomad4 SAS

AF:

0.0141

Gnomad4 FIN

AF:

0.0378

Gnomad4 NFE

AF:

0.0587

Gnomad4 OTH

AF:

0.0365

Alfa

AF:

0.0444

Hom.:

359

Bravo

AF:

0.0332

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 06, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinitis pigmentosa 3

Benign:1

Nov 07, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Macular degeneration, X-linked atrophic

Benign:1

Nov 07, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

X-linked cone-rod dystrophy 1

Benign:1

Nov 07, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.034

DANN

Benign

0.16

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