rs5918520

Variant names:

• chrX-38291125-T-A
• rs5918520
• NM_001034853.2:c.1507-101A>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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 reviewed by expert panel B:3
• Conservation: PhyloP100: -0.283
• Publications: 4 publications found

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]

RPGR Gene-Disease associations (from GenCC):

• retinitis pigmentosa 3

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
• RPGR-related retinopathy

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• primary ciliary dyskinesia-retinitis pigmentosa syndrome

  Inheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• cone-rod dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• macular degeneration, X-linked atrophic

  Inheritance: XL Classification: LIMITED Submitted by: G2P

ENSG00000250349 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1286105.Status of the report is reviewed_by_expert_panel, 3 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001034853.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPGR	NM_001034853.2	MANE Select	c.1507-101A>T		intron	N/A	NP_001030025.1	Q92834-6
	RPGR	NM_000328.3		c.1507-101A>T		intron	N/A	NP_000319.1	Q92834-2
	RPGR	NM_001367245.1		c.1504-101A>T		intron	N/A	NP_001354174.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPGR	ENST00000645032.1	MANE Select	c.1507-101A>T		intron	N/A	ENSP00000495537.1	Q92834-6
	ENSG00000250349	ENST00000465127.1	TSL:5	c.172-374996T>A		intron	N/A	ENSP00000417050.1	B4E171
	RPGR	ENST00000339363.7	TSL:5	c.1507-101A>T		intron	N/A	ENSP00000343671.3	Q92834-1

Frequencies

GnomAD3 genomes AF: 0.295 AC: 27591 AN: 93675 Hom.: 2913 Cov.: 19

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

African (AFR) AF: 0.208 AC: 262 AN: 1259

American (AMR) AF: 0.358 AC: 567 AN: 1584

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 690 AN: 2145

East Asian (EAS) AF: 0.585 AC: 1619 AN: 2767

South Asian (SAS) AF: 0.383 AC: 617 AN: 1613

European-Finnish (FIN) AF: 0.237 AC: 2198 AN: 9264

Middle Eastern (MID) AF: 0.229 AC: 56 AN: 245

European-Non Finnish (NFE) AF: 0.232 AC: 9941 AN: 42912

Other (OTH) AF: 0.275 AC: 862 AN: 3134

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

African (AFR) AF: 0.281 AC: 6646 AN: 23618

American (AMR) AF: 0.352 AC: 2864 AN: 8140

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 794 AN: 2388

East Asian (EAS) AF: 0.623 AC: 1976 AN: 3173

South Asian (SAS) AF: 0.397 AC: 807 AN: 2035

European-Finnish (FIN) AF: 0.219 AC: 718 AN: 3285

Middle Eastern (MID) AF: 0.287 AC: 52 AN: 181

European-Non Finnish (NFE) AF: 0.269 AC: 13184 AN: 48997

Other (OTH) AF: 0.314 AC: 397 AN: 1265

Alfa AF: 0.0584 Hom.: 221

Bravo AF: 0.276

ClinVar

ClinVar submissions

Significance: Benign

Revision: reviewed by expert panel

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	RPGR-related retinopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.15
DANN	Benign	0.067
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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