rs2071093

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

congenital stationary night blindness autosomal dominant 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
retinitis pigmentosa 4
Inheritance: AD, AR, SD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
congenital stationary night blindness
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
fundus albipunctatus
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

RHO links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
RHO	NM_000539.3 link	c.*43C>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000296271.4	NP_000530.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHO	ENST00000296271.4 link	c.*43C>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_000539.3	ENSP00000296271.3

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

GnomAD2 exomes

AF:

0.0813

AC:

20150

AN:

247754

AF XY:

0.0854

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 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

African (AFR)

AF:

0.0701

AC:

1962

AN:

27980

American (AMR)

AF:

0.0582

AC:

2583

AN:

44346

Ashkenazi Jewish (ASJ)

AF:

0.164

AC:

4024

AN:

24512

East Asian (EAS)

AF:

0.0491

AC:

1883

AN:

38340

South Asian (SAS)

AF:

0.118

AC:

9519

AN:

80704

European-Finnish (FIN)

AF:

0.0382

AC:

1977

AN:

51736

Middle Eastern (MID)

AF:

0.130

AC:

661

AN:

5074

European-Non Finnish (NFE)

AF:

0.0871

AC:

74714

AN:

857312

Other (OTH)

AF:

0.0946

AC:

4842

AN:

51194

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

5156

10312

15467

20623

25779

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2532

5064

7596

10128

12660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0775

AC:

11800

AN:

152248

Hom.:

512

Cov.:

AF XY:

0.0771

AC XY:

5738

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.0687

AC:

2856

AN:

41544

American (AMR)

AF:

0.0769

AC:

1176

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.161

AC:

558

AN:

3468

East Asian (EAS)

AF:

0.0627

AC:

325

AN:

5182

South Asian (SAS)

AF:

0.107

AC:

516

AN:

4822

European-Finnish (FIN)

AF:

0.0382

AC:

405

AN:

10616

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0839

AC:

5706

AN:

68002

Other (OTH)

AF:

0.0960

AC:

203

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

543

1086

1628

2171

2714

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

134

268

402

536

670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0701

Hom.:

223

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

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Pigmentary retinal dystrophy

Benign:1

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Retinitis pigmentosa 4

Benign:1

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Congenital stationary night blindness autosomal dominant 1

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

3.0

(source)

DANN

Benign

0.68

PhyloP100

0.17

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over