rs5918520

Positions:

• chrX-38291125-T-A
• chrX-38291125-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001034853.2(RPGR):​c.1507-101A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 158,578 control chromosomes in the GnomAD database, including 4,584 homozygotes. There are 11,532 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.29 (2915 hom., 7318 hem., cov: 19)
  • Exomes 𝑓: 0.26 (1669 hom. 4214 hem.)
• Consequence: RPGR NM_001034853.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.283

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant X-38291125-T-A is Benign according to our data. Variant chrX-38291125-T-A is described in ClinVar as [Benign]. Clinvar id is 1286105.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPGR	NM_001034853.2	c.1507-101A>T		intron_variant		ENST00000645032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPGR	ENST00000645032.1	c.1507-101A>T		intron_variant			NM_001034853.2	A2

Frequencies

GnomAD3 genomes AF: 0.295 AC: 27591 AN: 93675 Hom.: 2913 Cov.: 19 AF XY: 0.283 AC XY: 7320 AN XY: 25901

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.308

GnomAD4 exome AF: 0.259 AC: 16812 AN: 64923 Hom.: 1669 AF XY: 0.281 AC XY: 4214 AN XY: 14995

Gnomad4 AFR exome AF: 0.208

Gnomad4 AMR exome AF: 0.358

Gnomad4 ASJ exome AF: 0.322

Gnomad4 EAS exome AF: 0.585

Gnomad4 SAS exome AF: 0.383

Gnomad4 FIN exome AF: 0.237

Gnomad4 NFE exome AF: 0.232

Gnomad4 OTH exome AF: 0.275

GnomAD4 genome AF: 0.295 AC: 27591 AN: 93655 Hom.: 2915 Cov.: 19 AF XY: 0.283 AC XY: 7318 AN XY: 25897

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.332

Gnomad4 EAS AF: 0.623

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.314

Alfa AF: 0.0584 Hom.: 221

Bravo AF: 0.276

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 05, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.15
DANN	Benign	0.067

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: rs5918520; hg19: chrX-38150378; COSMIC: COSV58840366;