Variant rs2071093 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_000539.3(RHO):c.*43C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0855 in 1,333,446 control chromosomes in the GnomAD database, including 5,324 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.078 ( 512 hom., cov: 32)

Exomes 𝑓: 0.086 ( 4812 hom. )

Consequence

RHO
NM_000539.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.175

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 3-129533761-C-A is Benign according to our data. Variant chr3-129533761-C-A is described in ClinVar as [Benign]. Clinvar id is 256382.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHO	NM_000539.3 linkuse as main transcript	c.*43C>A		3_prime_UTR_variant	5/5	ENST00000296271.4	NP_000530.1	P08100

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHO	ENST00000296271.4 linkuse as main transcript	c.*43C>A		3_prime_UTR_variant	5/5	1	NM_000539.3	ENSP00000296271.3		P08100

Frequencies

GnomAD3 genomes

AF:

0.0775

AC:

11786

AN:

152130

Hom.:

511

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0686

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.0770

Gnomad ASJ

AF:

0.161

Gnomad EAS

AF:

0.0631

Gnomad SAS

AF:

0.107

Gnomad FIN

AF:

0.0382

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0839

Gnomad OTH

AF:

0.0951

GnomAD3 exomes

AF:

0.0813

AC:

20150

AN:

247754

Hom.:

917

AF XY:

0.0854

AC XY:

11476

AN XY:

134366

show subpopulations

Gnomad AFR exome

AF:

0.0709

Gnomad AMR exome

AF:

0.0562

Gnomad ASJ exome

AF:

0.163

Gnomad EAS exome

AF:

0.0632

Gnomad SAS exome

AF:

0.115

Gnomad FIN exome

AF:

0.0367

Gnomad NFE exome

AF:

0.0842

Gnomad OTH exome

AF:

0.0997

GnomAD4 exome

AF:

0.0865

AC:

102165

AN:

1181198

Hom.:

4812

Cov.:

AF XY:

0.0885

AC XY:

53245

AN XY:

601450

show subpopulations

Gnomad4 AFR exome

AF:

0.0701

Gnomad4 AMR exome

AF:

0.0582

Gnomad4 ASJ exome

AF:

0.164

Gnomad4 EAS exome

AF:

0.0491

Gnomad4 SAS exome

AF:

0.118

Gnomad4 FIN exome

AF:

0.0382

Gnomad4 NFE exome

AF:

0.0871

Gnomad4 OTH exome

AF:

0.0946

GnomAD4 genome

AF:

0.0775

AC:

11800

AN:

152248

Hom.:

512

Cov.:

AF XY:

0.0771

AC XY:

5738

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0687

Gnomad4 AMR

AF:

0.0769

Gnomad4 ASJ

AF:

0.161

Gnomad4 EAS

AF:

0.0627

Gnomad4 SAS

AF:

0.107

Gnomad4 FIN

AF:

0.0382

Gnomad4 NFE

AF:

0.0839

Gnomad4 OTH

AF:

0.0960

Alfa

AF:

0.0633

Hom.:

118

Bravo

AF:

0.0797

Asia WGS

AF:

0.106

AC:

371

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

- -

Congenital stationary night blindness autosomal dominant 1

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. -

Retinitis pigmentosa

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

BayesDel_noAF

Benign

-0.42

CADD

Benign

3.0

DANN

Benign

0.68

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