rs41312110

Positions:

• chrX-38275043-G-A

Variant summary

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

The ENST00000339363.7(RPGR):​c.2764+46C>T 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: RPGR ENST00000339363.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.39

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]

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	UniProt
RPGR	NM_000328.3	c.2149+46C>T		intron_variant
RPGR	NM_001367245.1	c.2146+46C>T		intron_variant
RPGR	NM_001367246.1	c.1963+46C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPGR	ENST00000339363.7	c.2764+46C>T		intron_variant		5		P4
RPGR	ENST00000494707.6	c.1197+46C>T		intron_variant		5
RPGR	ENST00000642395.2	c.2149+46C>T		intron_variant				A2

Frequencies

GnomAD3 genomes AF: 0.0362 AC: 4014 AN: 110956 Hom.: 87 Cov.: 22 AF XY: 0.0310 AC XY: 1031 AN XY: 33222

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

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.: 14 AF XY: 0.0474 AC XY: 11313 AN XY: 238542

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.: 87 Cov.: 22 AF XY: 0.0310 AC XY: 1032 AN XY: 33280

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:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Retinitis pigmentosa 3 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Macular degeneration, X-linked atrophic Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 06, 2018

- -

X-linked cone-rod dystrophy 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

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

Other links and lift over

dbSNP: rs41312110; hg19: chrX-38134296; COSMIC: COSV58841520; COSMIC: COSV58841520;