rs41312110

Variant names:

• chrX-38275043-G-A
• rs41312110
• ENST00000465127.1:c.172-391078G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-38275043-G-A
• chrX-38275043-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000328.3(RPGR):​c.2149+46C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0486 in 963,272 control chromosomes in the GnomAD database, including 1,001 homozygotes. There are 12,345 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.036 (87 hom., 1032 hem., cov: 22)
  • Exomes 𝑓: 0.050 (914 hom. 11313 hem.)
• Consequence: RPGR NM_000328.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.39
• Publications: 1 publications found

Genes affected

ENSG00000250349 (HGNC:):

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, Labcorp Genetics (formerly Invitae), Ambry Genetics
• RPGR-related retinopathy

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

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

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-38275043-G-A is Benign according to our data. Variant chrX-38275043-G-A is described in ClinVar as Benign. ClinVar VariationId is 255834.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.057 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000328.3. 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_000328.3		c.2149+46C>T		intron	N/A	NP_000319.1	Q92834-2
	RPGR	NM_001367245.1		c.2146+46C>T		intron	N/A	NP_001354174.1
	RPGR	NM_001367246.1		c.1963+46C>T		intron	N/A	NP_001354175.1	Q92834-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000250349	ENST00000465127.1	TSL:5	c.172-391078G>A		intron	N/A	ENSP00000417050.1	B4E171
	RPGR	ENST00000339363.7	TSL:5	c.2764+46C>T		intron	N/A	ENSP00000343671.3	Q92834-1
	RPGR	ENST00000642395.2		c.2149+46C>T		intron	N/A	ENSP00000493468.2	Q92834-2

Frequencies

GnomAD3 genomes AF: 0.0362 AC: 4014 AN: 110956 Hom.: 87 Cov.: 22

Gnomad AFR AF: 0.00750

Gnomad AMI AF: 0.0562

Gnomad AMR AF: 0.0225

Gnomad ASJ AF: 0.0353

Gnomad EAS AF: 0.000280

Gnomad SAS AF: 0.0133

Gnomad FIN AF: 0.0378

Gnomad MID AF: 0.0170

Gnomad NFE AF: 0.0587

Gnomad OTH AF: 0.0370

GnomAD2 exomes AF: 0.0372 AC: 6371 AN: 171074 AF XY: 0.0356

Gnomad AFR exome AF: 0.00632

Gnomad AMR exome AF: 0.0156

Gnomad ASJ exome AF: 0.0446

Gnomad EAS exome AF: 0.0000753

Gnomad FIN exome AF: 0.0424

Gnomad NFE exome AF: 0.0585

Gnomad OTH exome AF: 0.0358

GnomAD4 exome AF: 0.0502 AC: 42765 AN: 852268 Hom.: 914 Cov.: 14 AF XY: 0.0474 AC XY: 11313 AN XY: 238542

African (AFR) AF: 0.00613 AC: 133 AN: 21687

American (AMR) AF: 0.0158 AC: 546 AN: 34652

Ashkenazi Jewish (ASJ) AF: 0.0432 AC: 771 AN: 17863

East Asian (EAS) AF: 0.0000690 AC: 2 AN: 28986

South Asian (SAS) AF: 0.0233 AC: 1132 AN: 48677

European-Finnish (FIN) AF: 0.0455 AC: 1786 AN: 39222

Middle Eastern (MID) AF: 0.00979 AC: 35 AN: 3574

European-Non Finnish (NFE) AF: 0.0594 AC: 36787 AN: 619599

Other (OTH) AF: 0.0414 AC: 1573 AN: 38008

GnomAD4 genome AF: 0.0362 AC: 4016 AN: 111004 Hom.: 87 Cov.: 22 AF XY: 0.0310 AC XY: 1032 AN XY: 33280

African (AFR) AF: 0.00748 AC: 229 AN: 30615

American (AMR) AF: 0.0225 AC: 235 AN: 10459

Ashkenazi Jewish (ASJ) AF: 0.0353 AC: 93 AN: 2638

East Asian (EAS) AF: 0.000281 AC: 1 AN: 3563

South Asian (SAS) AF: 0.0141 AC: 37 AN: 2626

European-Finnish (FIN) AF: 0.0378 AC: 221 AN: 5840

Middle Eastern (MID) AF: 0.0140 AC: 3 AN: 214

European-Non Finnish (NFE) AF: 0.0587 AC: 3104 AN: 52867

Other (OTH) AF: 0.0365 AC: 55 AN: 1506

Alfa AF: 0.0444 Hom.: 359

Bravo AF: 0.0332

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Macular degeneration, X-linked atrophic (1)
-	-	1	not specified (1)
-	-	1	Retinitis pigmentosa 3 (1)
-	-	1	X-linked cone-rod dystrophy 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.034
DANN	Benign	0.16
PhyloP100		-1.4
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: rs41312110; hg19: chrX-38134296; COSMIC: COSV58841520; COSMIC: COSV58841520;