rs62635008

Positions:

• chrX-38290948-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001034853.2(RPGR):​c.1572+11A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0649 in 952,665 control chromosomes in the GnomAD database, including 2,328 homozygotes. There are 17,309 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.094 (509 hom., 2926 hem., cov: 21)
  • Exomes 𝑓: 0.061 (1819 hom. 14383 hem.)
• Consequence: RPGR NM_001034853.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7 O:1
• Conservation: PhyloP100: -1.07

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=-0.93).
• BP6: Variant X-38290948-T-C is Benign according to our data. Variant chrX-38290948-T-C is described in ClinVar as [Benign]. Clinvar id is 92852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-38290948-T-C is described in Lovd as [Likely_benign]. Variant chrX-38290948-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPGR	NM_001034853.2	c.1572+11A>G		intron_variant		ENST00000645032.1	NP_001030025.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPGR	ENST00000645032.1	c.1572+11A>G		intron_variant			NM_001034853.2	ENSP00000495537.1
ENSG00000250349	ENST00000465127.1	c.172-375173T>C		intron_variant		5		ENSP00000417050.1

Frequencies

GnomAD3 genomes AF: 0.0941 AC: 10285 AN: 109315 Hom.: 511 Cov.: 21 AF XY: 0.0919 AC XY: 2919 AN XY: 31767

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.0677

Gnomad EAS AF: 0.0753

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.0935

Gnomad MID AF: 0.0702

Gnomad NFE AF: 0.0490

Gnomad OTH AF: 0.0729

GnomAD3 exomes AF: 0.0985 AC: 16562 AN: 168178 Hom.: 974 AF XY: 0.0850 AC XY: 4796 AN XY: 56398

Gnomad AFR exome AF: 0.163

Gnomad AMR exome AF: 0.232

Gnomad ASJ exome AF: 0.0625

Gnomad EAS exome AF: 0.0677

Gnomad SAS exome AF: 0.147

Gnomad FIN exome AF: 0.0945

Gnomad NFE exome AF: 0.0460

Gnomad OTH exome AF: 0.0745

GnomAD4 exome AF: 0.0611 AC: 51506 AN: 843332 Hom.: 1819 Cov.: 12 AF XY: 0.0623 AC XY: 14383 AN XY: 230904

Gnomad4 AFR exome AF: 0.159

Gnomad4 AMR exome AF: 0.218

Gnomad4 ASJ exome AF: 0.0577

Gnomad4 EAS exome AF: 0.0770

Gnomad4 SAS exome AF: 0.139

Gnomad4 FIN exome AF: 0.0895

Gnomad4 NFE exome AF: 0.0422

Gnomad4 OTH exome AF: 0.0636

GnomAD4 genome AF: 0.0941 AC: 10291 AN: 109333 Hom.: 509 Cov.: 21 AF XY: 0.0920 AC XY: 2926 AN XY: 31795

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.0677

Gnomad4 EAS AF: 0.0756

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.0935

Gnomad4 NFE AF: 0.0490

Gnomad4 OTH AF: 0.0721

Alfa AF: 0.0696 Hom.: 540

Bravo AF: 0.104

ClinVar

Significance: Benign

Submissions summary: Benign:7 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

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 -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
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	Eurofins Ntd Llc (ga)	Aug 15, 2014	- -

not provided Benign:2 Other:1

not provided, no classification provided	literature only	Retina International	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -
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	-0.93
CADD	Benign	0.52
DANN	Benign	0.35

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: rs62635008; hg19: chrX-38150201; COSMIC: COSV58835966;