rs751710678

chrX-38286437-TCCTTCCTCCTCTTCCCCCTCC-TchrX-38286437-TCCTTCCTCCTCTTCCCCCTCC-TCCTTCCTCCTCTTCCCCCTCCCCTTCCTCCTCTTCCCCCTCC

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4 BP6_Very_Strong BA1

The NM_001034853.2(RPGR):c.2541_2561del(p.Glu850_Gly856del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0242 in 855,600 control chromosomes in the GnomAD database, including 589 homozygotes. There are 6,664 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G847G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0023 (1 hom., 0 hem., cov: 3)
  • Exomes 𝑓: 0.025 (588 hom. 6664 hem.)
• Consequence: RPGR NM_001034853.2 inframe_deletion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0290

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.

• PM4: Nonframeshift variant in NON repetitive region in NM_001034853.2.
• BP6: Variant X-38286437-TCCTTCCTCCTCTTCCCCCTCC-T is Benign according to our data. Variant chrX-38286437-TCCTTCCTCCTCTTCCCCCTCC-T is described in ClinVar as [Benign]. Clinvar id is 237685.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-38286437-TCCTTCCTCCTCTTCCCCCTCC-T is described in Lovd as [Likely_benign]. Variant chrX-38286437-TCCTTCCTCCTCTTCCCCCTCC-T is described in Lovd as [Benign].
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPGR	NM_001034853.2	c.2541_2561del	p.Glu850_Gly856del	inframe_deletion	15/15	ENST00000645032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPGR	ENST00000645032.1	c.2541_2561del	p.Glu850_Gly856del	inframe_deletion	15/15		NM_001034853.2	A2

Frequencies

GnomAD3 genomes AF: 0.00232 AC: 42 AN: 18068 Hom.: 1 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 1068

Gnomad AFR AF: 0.00242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00510

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0172

Gnomad FIN AF: 0.00920

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00136

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0224 AC: 1123 AN: 50113 Hom.: 62 AF XY: 0.0154 AC XY: 131 AN XY: 8523

Gnomad AFR exome AF: 0.0292

Gnomad AMR exome AF: 0.0314

Gnomad ASJ exome AF: 0.00187

Gnomad EAS exome AF: 0.0200

Gnomad SAS exome AF: 0.0330

Gnomad FIN exome AF: 0.0444

Gnomad NFE exome AF: 0.00751

Gnomad OTH exome AF: 0.0120

GnomAD4 exome AF: 0.0246 AC: 20632 AN: 837520 Hom.: 588 AF XY: 0.0282 AC XY: 6664 AN XY: 236558

Gnomad4 AFR exome AF: 0.0689

Gnomad4 AMR exome AF: 0.0891

Gnomad4 ASJ exome AF: 0.0403

Gnomad4 EAS exome AF: 0.0878

Gnomad4 SAS exome AF: 0.0849

Gnomad4 FIN exome AF: 0.0869

Gnomad4 NFE exome AF: 0.0143

Gnomad4 OTH exome AF: 0.0357

GnomAD4 genome AF: 0.00232 AC: 42 AN: 18080 Hom.: 1 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 1072

Gnomad4 AFR AF: 0.00242

Gnomad4 AMR AF: 0.00511

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0172

Gnomad4 FIN AF: 0.00920

Gnomad4 NFE AF: 0.00136

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0103 Hom.: 70

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 25, 2015

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 31, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs751710678; hg19: chrX-38145690;