rs7984

Variant summary

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

The NM_000539.3(RHO):c.-26A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,613,362 control chromosomes in the GnomAD database, including 61,563 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 17743 hom., cov: 32)

Exomes 𝑓: 0.20 ( 43820 hom. )

Consequence

RHO
NM_000539.3 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.33

Variant links:

Genes affected

RHO (HGNC:10012): (rhodopsin) The protein encoded by this gene is found in rod cells in the back of the eye and is essential for vision in low-light conditions. The encoded protein binds to 11-cis retinal and is activated when light hits the retinal molecule. Defects in this gene are a cause of congenital stationary night blindness. [provided by RefSeq, Aug 2017]

RHO 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 (BayesDel_noAF=-0.9).

BP6

Variant 3-129528708-A-G is Benign according to our data. Variant chr3-129528708-A-G is described in ClinVar as [Benign]. Clinvar id is 256383.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-129528708-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RHO	NM_000539.3 linkuse as main transcript	c.-26A>G		5_prime_UTR_variant	1/5	ENST00000296271.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RHO	ENST00000296271.4 linkuse as main transcript	c.-26A>G		5_prime_UTR_variant	1/5	1	NM_000539.3	P1

Frequencies

GnomAD3 genomes

AF:

0.378

AC:

57383

AN:

151928

Hom.:

17682

Cov.:

show subpopulations

Gnomad AFR

AF:

0.826

Gnomad AMI

AF:

0.179

Gnomad AMR

AF:

0.342

Gnomad ASJ

AF:

0.286

Gnomad EAS

AF:

0.633

Gnomad SAS

AF:

0.383

Gnomad FIN

AF:

0.0702

Gnomad MID

AF:

0.287

Gnomad NFE

AF:

0.150

Gnomad OTH

AF:

0.344

GnomAD3 exomes

AF:

0.277

AC:

69244

AN:

250244

Hom.:

15154

AF XY:

0.268

AC XY:

36285

AN XY:

135386

show subpopulations

Gnomad AFR exome

AF:

0.838

Gnomad AMR exome

AF:

0.277

Gnomad ASJ exome

AF:

0.276

Gnomad EAS exome

AF:

0.637

Gnomad SAS exome

AF:

0.379

Gnomad FIN exome

AF:

0.0668

Gnomad NFE exome

AF:

0.153

Gnomad OTH exome

AF:

0.243

GnomAD4 exome

AF:

0.200

AC:

291721

AN:

1461316

Hom.:

43820

Cov.:

AF XY:

0.204

AC XY:

148025

AN XY:

726934

show subpopulations

Gnomad4 AFR exome

AF:

0.853

Gnomad4 AMR exome

AF:

0.281

Gnomad4 ASJ exome

AF:

0.279

Gnomad4 EAS exome

AF:

0.589

Gnomad4 SAS exome

AF:

0.379

Gnomad4 FIN exome

AF:

0.0703

Gnomad4 NFE exome

AF:

0.150

Gnomad4 OTH exome

AF:

0.255

GnomAD4 genome

AF:

0.378

AC:

57507

AN:

152046

Hom.:

17743

Cov.:

AF XY:

0.378

AC XY:

28116

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.826

Gnomad4 AMR

AF:

0.342

Gnomad4 ASJ

AF:

0.286

Gnomad4 EAS

AF:

0.632

Gnomad4 SAS

AF:

0.383

Gnomad4 FIN

AF:

0.0702

Gnomad4 NFE

AF:

0.150

Gnomad4 OTH

AF:

0.345

Alfa

AF:

0.279

Hom.:

2191

Bravo

AF:

0.417

Asia WGS

AF:

0.505

AC:

1760

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Pigmentary retinal dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Retinitis pigmentosa 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Congenital stationary night blindness autosomal dominant 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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. -

Retinitis pigmentosa

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

Cadd

Benign

0.56

Dann

Benign

0.29

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