rs74034910

Variant summary

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

The NM_020366.4(RPGRIP1):c.1793G>A(p.Arg598Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0027 in 1,613,758 control chromosomes in the GnomAD database, including 94 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 48 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 46 hom. )

Consequence

RPGRIP1
NM_020366.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.399

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=0.002028197).

BP6

Variant 14-21324648-G-A is Benign according to our data. Variant chr14-21324648-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 235620.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-21324648-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPGRIP1	NM_020366.4 linkuse as main transcript	c.1793G>A	p.Arg598Gln	missense_variant	15/25	ENST00000400017.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPGRIP1	ENST00000400017.7 linkuse as main transcript	c.1793G>A	p.Arg598Gln	missense_variant	15/25	1	NM_020366.4	P2	Q96KN7-1

Frequencies

GnomAD3 genomes

AF:

0.0149

AC:

2271

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0521

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00445

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.00357

AC:

889

AN:

249082

Hom.:

AF XY:

0.00264

AC XY:

357

AN XY:

135168

show subpopulations

Gnomad AFR exome

AF:

0.0502

Gnomad AMR exome

AF:

0.00232

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.00215

GnomAD4 exome

AF:

0.00143

AC:

2092

AN:

1461518

Hom.:

Cov.:

AF XY:

0.00117

AC XY:

853

AN XY:

727064

show subpopulations

Gnomad4 AFR exome

AF:

0.0520

Gnomad4 AMR exome

AF:

0.00250

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000513

Gnomad4 OTH exome

AF:

0.00267

GnomAD4 genome

AF:

0.0149

AC:

2270

AN:

152240

Hom.:

Cov.:

AF XY:

0.0143

AC XY:

1061

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0519

Gnomad4 AMR

AF:

0.00445

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.00200

Hom.:

Bravo

AF:

0.0166

ESP6500AA

AF:

0.0455

AC:

178

ESP6500EA

AF:

0.000241

AC:

ExAC

AF:

0.00423

AC:

511

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Feb 18, 2022	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 14, 2016	- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 23, 2024

- -

Leber congenital amaurosis 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

Cone-rod dystrophy 13

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 28, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

May 19, 2016

- -

Leber congenital amaurosis 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 28, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.46

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.028

T;T;T;.

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.75

T;T;T;T

MetaRNN

Benign

0.0020

T;T;T;T

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

N;N;N;N;N;N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.5

N;N;N;N

REVEL

Benign

0.068

Sift

Benign

0.074

T;T;T;T

Sift4G

Benign

0.29

T;T;T;T

Polyphen

0.41, 0.36

.;B;B;.

Vest4

0.74

MVP

0.78

MPC

0.082

ClinPred

0.0087

GERP RS

1.3

Varity_R

0.053

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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