rs80178653

Positions:

• chrX-38301222-A-G

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.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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.684

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=-0.77).
• 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	UniProt
RPGR	NM_001034853.2	c.1059+25T>C		intron_variant		ENST00000645032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPGR	ENST00000645032.1	c.1059+25T>C		intron_variant			NM_001034853.2	A2

Frequencies

GnomAD3 genomes AF: 0.0312 AC: 3480 AN: 111660 Hom.: 93 Cov.: 22 AF XY: 0.0356 AC XY: 1205 AN XY: 33834

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

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.: 23 AF XY: 0.0378 AC XY: 12281 AN XY: 324502

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.: 92 Cov.: 22 AF XY: 0.0357 AC XY: 1209 AN XY: 33900

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:2

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

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

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

Other links and lift over

dbSNP: rs80178653; hg19: chrX-38160475;