rs1040904

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020366.4(RPGRIP1):c.287C>A(p.Pro96Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0489 in 1,612,406 control chromosomes in the GnomAD database, including 3,144 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.057 ( 370 hom., cov: 31)

Exomes 𝑓: 0.048 ( 2774 hom. )

Consequence

RPGRIP1
NM_020366.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: 0.480

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026779473).

BP6

Variant 14-21301034-C-A is Benign according to our data. Variant chr14-21301034-C-A is described in ClinVar as [Benign]. Clinvar id is 99819.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-21301034-C-A is described in Lovd as [Benign]. Variant chr14-21301034-C-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPGRIP1	NM_020366.4 linkuse as main transcript	c.287C>A	p.Pro96Gln	missense_variant	4/25	ENST00000400017.7	NP_065099.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPGRIP1	ENST00000400017.7 linkuse as main transcript	c.287C>A	p.Pro96Gln	missense_variant	4/25	1	NM_020366.4	ENSP00000382895	P2	Q96KN7-1
RPGRIP1	ENST00000557771.5 linkuse as main transcript	c.287C>A	p.Pro96Gln	missense_variant	3/24	5		ENSP00000451219	A2
RPGRIP1	ENST00000556336.5 linkuse as main transcript	c.287C>A	p.Pro96Gln	missense_variant	3/21	5		ENSP00000450445

Frequencies

GnomAD3 genomes

AF:

0.0570

AC:

8677

AN:

152180

Hom.:

363

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0562

Gnomad AMI

AF:

0.120

Gnomad AMR

AF:

0.158

Gnomad ASJ

AF:

0.0608

Gnomad EAS

AF:

0.0349

Gnomad SAS

AF:

0.0339

Gnomad FIN

AF:

0.0272

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0420

Gnomad OTH

AF:

0.0459

GnomAD3 exomes

AF:

0.0709

AC:

17194

AN:

242586

Hom.:

1429

AF XY:

0.0627

AC XY:

8334

AN XY:

132852

show subpopulations

Gnomad AFR exome

AF:

0.0522

Gnomad AMR exome

AF:

0.252

Gnomad ASJ exome

AF:

0.0581

Gnomad EAS exome

AF:

0.0355

Gnomad SAS exome

AF:

0.0355

Gnomad FIN exome

AF:

0.0283

Gnomad NFE exome

AF:

0.0419

Gnomad OTH exome

AF:

0.0609

GnomAD4 exome

AF:

0.0481

AC:

70169

AN:

1460108

Hom.:

2774

Cov.:

AF XY:

0.0468

AC XY:

33975

AN XY:

726328

show subpopulations

Gnomad4 AFR exome

AF:

0.0531

Gnomad4 AMR exome

AF:

0.239

Gnomad4 ASJ exome

AF:

0.0561

Gnomad4 EAS exome

AF:

0.0296

Gnomad4 SAS exome

AF:

0.0348

Gnomad4 FIN exome

AF:

0.0272

Gnomad4 NFE exome

AF:

0.0427

Gnomad4 OTH exome

AF:

0.0466

GnomAD4 genome

AF:

0.0572

AC:

8706

AN:

152298

Hom.:

370

Cov.:

AF XY:

0.0574

AC XY:

4276

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0565

Gnomad4 AMR

AF:

0.159

Gnomad4 ASJ

AF:

0.0608

Gnomad4 EAS

AF:

0.0350

Gnomad4 SAS

AF:

0.0337

Gnomad4 FIN

AF:

0.0272

Gnomad4 NFE

AF:

0.0420

Gnomad4 OTH

AF:

0.0454

Alfa

AF:

0.0480

Hom.:

Bravo

AF:

0.0686

TwinsUK

AF:

0.0472

AC:

175

ALSPAC

AF:

0.0324

AC:

125

ESP6500AA

AF:

0.0535

AC:

204

ESP6500EA

AF:

0.0390

AC:

317

ExAC

AF:

0.0604

AC:

7254

Asia WGS

AF:

0.0460

AC:

162

AN:

3478

EpiCase

AF:

0.0419

EpiControl

AF:

0.0485

ClinVar

Significance: Benign

Submissions summary: Benign:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2Other:1

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
not provided, no classification provided	literature only	Retina International	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 28, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Cone-rod dystrophy 13

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

2.0

DANN

Benign

0.70

DEOGEN2

Benign

0.0023

T;T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0022

LIST_S2

Benign

0.42

T;T;T

MetaRNN

Benign

0.0027

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.76

.;.;N

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.40

PROVEAN

Benign

2.0

N;N;N

REVEL

Benign

0.068

Sift

Benign

0.96

T;T;T

Sift4G

Benign

0.64

T;T;T

Polyphen

0.0070

.;.;B

Vest4

0.088

MPC

0.062

ClinPred

0.00052

GERP RS

-0.43

Varity_R

0.025

gMVP

0.068

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over