rs199625400

Positions:

• chrX-38310602-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001034853.2(RPGR):​c.778+13T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00854 in 1,208,155 control chromosomes in the GnomAD database, including 53 homozygotes. There are 3,280 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0063 (6 hom., 185 hem., cov: 22)
  • Exomes 𝑓: 0.0088 (47 hom. 3095 hem.)
• Consequence: RPGR NM_001034853.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.249

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]

ENSG00000250349 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant X-38310602-A-T is Benign according to our data. Variant chrX-38310602-A-T is described in ClinVar as [Benign]. Clinvar id is 504833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00626 (697/111420) while in subpopulation AMR AF= 0.0106 (111/10494). AF 95% confidence interval is 0.00898. There are 6 homozygotes in gnomad4. There are 185 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 6 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPGR	NM_001034853.2	c.778+13T>A		intron_variant		ENST00000645032.1	NP_001030025.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPGR	ENST00000645032.1	c.778+13T>A		intron_variant			NM_001034853.2	ENSP00000495537.1
ENSG00000250349	ENST00000465127.1	c.172-355519A>T		intron_variant		5		ENSP00000417050.1

Frequencies

GnomAD3 genomes AF: 0.00626 AC: 697 AN: 111362 Hom.: 6 Cov.: 22 AF XY: 0.00551 AC XY: 185 AN XY: 33560

Gnomad AFR AF: 0.00127

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0106

Gnomad ASJ AF: 0.0193

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00134

Gnomad MID AF: 0.0340

Gnomad NFE AF: 0.00887

Gnomad OTH AF: 0.00675

GnomAD3 exomes AF: 0.00605 AC: 1106 AN: 182703 Hom.: 5 AF XY: 0.00610 AC XY: 410 AN XY: 67245

Gnomad AFR exome AF: 0.00114

Gnomad AMR exome AF: 0.00439

Gnomad ASJ exome AF: 0.0205

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00158

Gnomad FIN exome AF: 0.00182

Gnomad NFE exome AF: 0.00885

Gnomad OTH exome AF: 0.00841

GnomAD4 exome AF: 0.00877 AC: 9621 AN: 1096735 Hom.: 47 Cov.: 30 AF XY: 0.00855 AC XY: 3095 AN XY: 362181

Gnomad4 AFR exome AF: 0.00144

Gnomad4 AMR exome AF: 0.00472

Gnomad4 ASJ exome AF: 0.0189

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00131

Gnomad4 FIN exome AF: 0.00225

Gnomad4 NFE exome AF: 0.0100

Gnomad4 OTH exome AF: 0.00793

GnomAD4 genome AF: 0.00626 AC: 697 AN: 111420 Hom.: 6 Cov.: 22 AF XY: 0.00550 AC XY: 185 AN XY: 33628

Gnomad4 AFR AF: 0.00127

Gnomad4 AMR AF: 0.0106

Gnomad4 ASJ AF: 0.0193

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00134

Gnomad4 NFE AF: 0.00887

Gnomad4 OTH AF: 0.00666

Alfa AF: 0.00910 Hom.: 69

Bravo AF: 0.00643

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Jan 11, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 24, 2014	778+13T>A in intron 7 of RPGR: This variant is not expected to have clinical sig nificance because it is not located within the conserved splice consensus sequen ce. It has been identified in 0.9% (59/6728) of European American chromosomes fr om a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washi ngton.edu/EVS; dbSNP rs199625400). -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	Sep 15, 2016	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Primary ciliary dyskinesia Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.89
DANN	Benign	0.71

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

Other links and lift over

dbSNP: rs199625400; hg19: chrX-38169855;