rs9322965

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_020366.4(RPGRIP1):c.1797G>A(p.Pro599Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 1,613,316 control chromosomes in the GnomAD database, including 44,140 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 3898 hom., cov: 32)

Exomes 𝑓: 0.23 ( 40242 hom. )

Consequence

RPGRIP1
NM_020366.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8O:1

Conservation

PhyloP100: -0.372

Publications

16 publications found

Variant links:

Genes affected

RPGRIP1 (HGNC:13436): (RPGR interacting protein 1) This gene encodes a photoreceptor protein that interacts with retinitis pigmentosa GTPase regulator protein and is a key component of cone and rod photoreceptor cells. Mutations in this gene lead to autosomal recessive congenital blindness. [provided by RefSeq, Oct 2008]

RPGRIP1 Gene-Disease associations (from GenCC):

cone-rod dystrophy 13
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
Leber congenital amaurosis 6
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
cone-rod dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Leber congenital amaurosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

RPGRIP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.139).

BP6

Variant 14-21324652-G-A is Benign according to our data. Variant chr14-21324652-G-A is described in ClinVar as Benign. ClinVar VariationId is 99812.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.372 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPGRIP1	NM_020366.4 link	c.1797G>A	p.Pro599Pro	synonymous_variant	Exon 15 of 25	ENST00000400017.7	NP_065099.3	Q96KN7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPGRIP1	ENST00000400017.7 link	c.1797G>A	p.Pro599Pro	synonymous_variant	Exon 15 of 25	1	NM_020366.4	ENSP00000382895.2		Q96KN7-1

Frequencies

GnomAD3 genomes

AF:

0.220

AC:

33490

AN:

152024

Hom.:

3899

Cov.:

show subpopulations

Gnomad AFR

AF:

0.228

Gnomad AMI

AF:

0.231

Gnomad AMR

AF:

0.146

Gnomad ASJ

AF:

0.184

Gnomad EAS

AF:

0.0187

Gnomad SAS

AF:

0.265

Gnomad FIN

AF:

0.256

Gnomad MID

AF:

0.271

Gnomad NFE

AF:

0.241

Gnomad OTH

AF:

0.205

GnomAD2 exomes

AF:

0.207

AC:

51517

AN:

249100

AF XY:

0.214

show subpopulations

Gnomad AFR exome

AF:

0.226

Gnomad AMR exome

AF:

0.105

Gnomad ASJ exome

AF:

0.185

Gnomad EAS exome

AF:

0.0159

Gnomad FIN exome

AF:

0.259

Gnomad NFE exome

AF:

0.239

Gnomad OTH exome

AF:

0.217

GnomAD4 exome

AF:

0.230

AC:

335615

AN:

1461174

Hom.:

40242

Cov.:

AF XY:

0.231

AC XY:

167974

AN XY:

726906

show subpopulations

African (AFR)

AF:

0.225

AC:

7545

AN:

33470

American (AMR)

AF:

0.113

AC:

5056

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.179

AC:

4674

AN:

26132

East Asian (EAS)

AF:

0.0195

AC:

775

AN:

39700

South Asian (SAS)

AF:

0.273

AC:

23511

AN:

86246

European-Finnish (FIN)

AF:

0.262

AC:

13939

AN:

53270

Middle Eastern (MID)

AF:

0.237

AC:

1365

AN:

5768

European-Non Finnish (NFE)

AF:

0.239

AC:

265119

AN:

1111506

Other (OTH)

AF:

0.226

AC:

13631

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

13995

27989

41984

55978

69973

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8910

17820

26730

35640

44550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.220

AC:

33522

AN:

152142

Hom.:

3898

Cov.:

AF XY:

0.219

AC XY:

16282

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.228

AC:

9482

AN:

41516

American (AMR)

AF:

0.146

AC:

2231

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.184

AC:

639

AN:

3470

East Asian (EAS)

AF:

0.0187

AC:

AN:

5188

South Asian (SAS)

AF:

0.266

AC:

1281

AN:

4818

European-Finnish (FIN)

AF:

0.256

AC:

2702

AN:

10574

Middle Eastern (MID)

AF:

0.264

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.241

AC:

16364

AN:

67988

Other (OTH)

AF:

0.208

AC:

439

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1341

2682

4024

5365

6706

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

360

720

1080

1440

1800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.228

Hom.:

13494

Bravo

AF:

0.209

Asia WGS

AF:

0.176

AC:

614

AN:

3478

EpiCase

AF:

0.232

EpiControl

AF:

0.227

ClinVar

Significance: Benign

Submissions summary: Benign:8Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Oct 21, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1Other:1

Retina International

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Leber congenital amaurosis 6;C2750720:Cone-rod dystrophy 13

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cone-rod dystrophy 13

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Leber congenital amaurosis 6

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_noAF

Benign

-0.75

CADD

Benign

6.9

(source)

DANN

Benign

0.86

PhyloP100

-0.37

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over