rs45486397

Variant names:

• chrX-38310814-A-G
• rs45486397
• NM_001034853.2:c.620-41T>C

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.620-41T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0142 in 1,174,410 control chromosomes in the GnomAD database, including 239 homozygotes. There are 5,265 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.032 (95 hom., 1004 hem., cov: 23)
  • Exomes 𝑓: 0.012 (144 hom. 4261 hem.)
• Consequence: RPGR NM_001034853.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3 O:1
• Conservation: PhyloP100: -0.302
• Publications: 0 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=-0.82).
• BP6: Variant X-38310814-A-G is Benign according to our data. Variant chrX-38310814-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 98793.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0882 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.620-41T>C		intron	N/A	NP_001030025.1	Q92834-6
	RPGR	NM_000328.3		c.620-41T>C		intron	N/A	NP_000319.1	Q92834-2
	RPGR	NM_001367245.1		c.620-44T>C		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.620-41T>C		intron	N/A	ENSP00000495537.1	Q92834-6
	ENSG00000250349	ENST00000465127.1	TSL:5	c.172-355307A>G		intron	N/A	ENSP00000417050.1	B4E171
	RPGR	ENST00000339363.7	TSL:5	c.620-41T>C		intron	N/A	ENSP00000343671.3	Q92834-1

Frequencies

GnomAD3 genomes AF: 0.0322 AC: 3614 AN: 112095 Hom.: 95 Cov.: 23

Gnomad AFR AF: 0.0911

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0195

Gnomad ASJ AF: 0.0140

Gnomad EAS AF: 0.000278

Gnomad SAS AF: 0.0156

Gnomad FIN AF: 0.00504

Gnomad MID AF: 0.0125

Gnomad NFE AF: 0.00838

Gnomad OTH AF: 0.0305

GnomAD2 exomes AF: 0.0163 AC: 2838 AN: 174074 AF XY: 0.0148

Gnomad AFR exome AF: 0.0954

Gnomad AMR exome AF: 0.00886

Gnomad ASJ exome AF: 0.0182

Gnomad EAS exome AF: 0.00104

Gnomad FIN exome AF: 0.00421

Gnomad NFE exome AF: 0.00910

Gnomad OTH exome AF: 0.0145

GnomAD4 exome AF: 0.0123 AC: 13071 AN: 1062259 Hom.: 144 Cov.: 25 AF XY: 0.0129 AC XY: 4261 AN XY: 331343

African (AFR) AF: 0.104 AC: 2687 AN: 25762

American (AMR) AF: 0.0104 AC: 364 AN: 34998

Ashkenazi Jewish (ASJ) AF: 0.0178 AC: 340 AN: 19118

East Asian (EAS) AF: 0.000634 AC: 19 AN: 29982

South Asian (SAS) AF: 0.0220 AC: 1163 AN: 52760

European-Finnish (FIN) AF: 0.00587 AC: 232 AN: 39519

Middle Eastern (MID) AF: 0.0163 AC: 52 AN: 3191

European-Non Finnish (NFE) AF: 0.00917 AC: 7446 AN: 812086

Other (OTH) AF: 0.0171 AC: 768 AN: 44843

GnomAD4 genome AF: 0.0322 AC: 3612 AN: 112151 Hom.: 95 Cov.: 23 AF XY: 0.0292 AC XY: 1004 AN XY: 34337

African (AFR) AF: 0.0910 AC: 2802 AN: 30803

American (AMR) AF: 0.0194 AC: 206 AN: 10626

Ashkenazi Jewish (ASJ) AF: 0.0140 AC: 37 AN: 2652

East Asian (EAS) AF: 0.000279 AC: 1 AN: 3586

South Asian (SAS) AF: 0.0156 AC: 42 AN: 2684

European-Finnish (FIN) AF: 0.00504 AC: 31 AN: 6152

Middle Eastern (MID) AF: 0.0137 AC: 3 AN: 219

European-Non Finnish (NFE) AF: 0.00836 AC: 445 AN: 53213

Other (OTH) AF: 0.0295 AC: 45 AN: 1528

Alfa AF: 0.0208 Hom.: 150

Bravo AF: 0.0381

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.4
DANN	Benign	0.67
PhyloP100		-0.30
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: rs45486397; hg19: chrX-38170067;