Variant chr3-129528683-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000539.3(RHO):c.-51G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.03 in 1,612,158 control chromosomes in the GnomAD database, including 5,409 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.084 ( 1361 hom., cov: 33)

Exomes 𝑓: 0.024 ( 4048 hom. )

Consequence

RHO
NM_000539.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.38

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=-0.64).

BP6

Variant 3-129528683-G-A is Benign according to our data. Variant chr3-129528683-G-A is described in ClinVar as [Benign]. Clinvar id is 343272.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.388 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.-51G>A		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.-51G>A		5_prime_UTR_variant	1/5	1	NM_000539.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0837

AC:

12729

AN:

152088

Hom.:

1359

Cov.:

show subpopulations

Gnomad AFR

AF:

0.186

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.153

Gnomad ASJ

AF:

0.00836

Gnomad EAS

AF:

0.403

Gnomad SAS

AF:

0.0321

Gnomad FIN

AF:

0.00358

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00363

Gnomad OTH

AF:

0.0693

GnomAD3 exomes

AF:

0.0701

AC:

17360

AN:

247792

Hom.:

2319

AF XY:

0.0596

AC XY:

8011

AN XY:

134456

show subpopulations

Gnomad AFR exome

AF:

0.187

Gnomad AMR exome

AF:

0.164

Gnomad ASJ exome

AF:

0.00549

Gnomad EAS exome

AF:

0.404

Gnomad SAS exome

AF:

0.0217

Gnomad FIN exome

AF:

0.00361

Gnomad NFE exome

AF:

0.00385

Gnomad OTH exome

AF:

0.0437

GnomAD4 exome

AF:

0.0243

AC:

35534

AN:

1459952

Hom.:

4048

Cov.:

AF XY:

0.0229

AC XY:

16630

AN XY:

726300

show subpopulations

Gnomad4 AFR exome

AF:

0.184

Gnomad4 AMR exome

AF:

0.160

Gnomad4 ASJ exome

AF:

0.00632

Gnomad4 EAS exome

AF:

0.357

Gnomad4 SAS exome

AF:

0.0223

Gnomad4 FIN exome

AF:

0.00331

Gnomad4 NFE exome

AF:

0.00280

Gnomad4 OTH exome

AF:

0.0441

GnomAD4 genome

AF:

0.0839

AC:

12771

AN:

152206

Hom.:

1361

Cov.:

AF XY:

0.0871

AC XY:

6479

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.186

Gnomad4 AMR

AF:

0.154

Gnomad4 ASJ

AF:

0.00836

Gnomad4 EAS

AF:

0.402

Gnomad4 SAS

AF:

0.0320

Gnomad4 FIN

AF:

0.00358

Gnomad4 NFE

AF:

0.00363

Gnomad4 OTH

AF:

0.0695

Alfa

AF:

0.0166

Hom.:

165

Bravo

AF:

0.101

Asia WGS

AF:

0.176

AC:

611

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

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	-	- -

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

-0.64

CADD

Benign

9.9

DANN

Benign

0.80

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