3-129532420-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000539.3(RHO):c.696+4C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0847 in 1,613,784 control chromosomes in the GnomAD database, including 6,274 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.078 ( 525 hom., cov: 32)

Exomes 𝑓: 0.085 ( 5749 hom. )

Consequence

RHO
NM_000539.3 splice_region, intron

Scores

Splicing: ADA: 0.00009567

Clinical Significance

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

Conservation

PhyloP100: -5.24

Publications

8 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 3-129532420-C-T is Benign according to our data. Variant chr3-129532420-C-T is described in ClinVar as Benign. ClinVar VariationId is 256384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHO	NM_000539.3 link	c.696+4C>T		splice_region_variant, intron_variant	Intron 3 of 4	ENST00000296271.4	NP_000530.1	P08100

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHO	ENST00000296271.4 link	c.696+4C>T		splice_region_variant, intron_variant	Intron 3 of 4	1	NM_000539.3	ENSP00000296271.3		P08100

Frequencies

GnomAD3 genomes

AF:

0.0780

AC:

11858

AN:

151988

Hom.:

524

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0698

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.0802

Gnomad ASJ

AF:

0.161

Gnomad EAS

AF:

0.0639

Gnomad SAS

AF:

0.108

Gnomad FIN

AF:

0.0374

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0836

Gnomad OTH

AF:

0.0946

GnomAD2 exomes

AF:

0.0815

AC:

20448

AN:

250880

AF XY:

0.0854

show subpopulations

Gnomad AFR exome

AF:

0.0716

Gnomad AMR exome

AF:

0.0600

Gnomad ASJ exome

AF:

0.163

Gnomad EAS exome

AF:

0.0634

Gnomad FIN exome

AF:

0.0360

Gnomad NFE exome

AF:

0.0837

Gnomad OTH exome

AF:

0.101

GnomAD4 exome

AF:

0.0854

AC:

124825

AN:

1461678

Hom.:

5749

Cov.:

AF XY:

0.0873

AC XY:

63481

AN XY:

727136

show subpopulations

African (AFR)

AF:

0.0691

AC:

2315

AN:

33480

American (AMR)

AF:

0.0621

AC:

2777

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.163

AC:

4267

AN:

26136

East Asian (EAS)

AF:

0.0510

AC:

2025

AN:

39700

South Asian (SAS)

AF:

0.118

AC:

10151

AN:

86258

European-Finnish (FIN)

AF:

0.0379

AC:

2018

AN:

53266

Middle Eastern (MID)

AF:

0.128

AC:

736

AN:

5768

European-Non Finnish (NFE)

AF:

0.0853

AC:

94889

AN:

1111962

Other (OTH)

AF:

0.0935

AC:

5647

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

7118

14235

21353

28470

35588

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3572

7144

10716

14288

17860

<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:

0.0781

AC:

11874

AN:

152106

Hom.:

525

Cov.:

AF XY:

0.0776

AC XY:

5770

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.0700

AC:

2905

AN:

41500

American (AMR)

AF:

0.0801

AC:

1225

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.161

AC:

560

AN:

3468

East Asian (EAS)

AF:

0.0635

AC:

327

AN:

5152

South Asian (SAS)

AF:

0.108

AC:

522

AN:

4822

European-Finnish (FIN)

AF:

0.0374

AC:

396

AN:

10590

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0836

AC:

5682

AN:

67968

Other (OTH)

AF:

0.0956

AC:

202

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

553

1105

1658

2210

2763

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:

0.0839

Hom.:

396

Bravo

AF:

0.0802

Asia WGS

AF:

0.106

AC:

372

AN:

3478

EpiCase

AF:

0.0953

EpiControl

AF:

0.0969

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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 12, 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 12, 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

-0.90

CADD

Benign

0.0020

(source)

DANN

Benign

0.64

PhyloP100

-5.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000096

dbscSNV1_RF

Benign

0.0020

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