Genetic Variant RHO:c.-51G>A (chr3-129528683-G-A) – ACMG Classification: Benign (-20 pts)

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.-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

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: Labcorp Genetics (formerly Invitae), G2P
inherited retinal dystrophy
Inheritance: SD, AD Classification: DEFINITIVE Submitted by: ClinGen
retinitis pigmentosa 4
Inheritance: SD, AR, AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
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=-0.64).

BP6

Variant 3-129528683-G-A is Benign according to our data. Variant chr3-129528683-G-A is described in ClinVar as Benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000539.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHO	NM_000539.3	MANE Select	c.-51G>A		5_prime_UTR	Exon 1 of 5	NP_000530.1	P08100

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHO	ENST00000296271.4	TSL:1 MANE Select	c.-51G>A		5_prime_UTR	Exon 1 of 5	ENSP00000296271.3	P08100

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

GnomAD2 exomes

AF:

0.0701

AC:

17360

AN:

247792

AF XY:

0.0596

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 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

African (AFR)

AF:

0.184

AC:

6140

AN:

33396

American (AMR)

AF:

0.160

AC:

7129

AN:

44592

Ashkenazi Jewish (ASJ)

AF:

0.00632

AC:

165

AN:

26120

East Asian (EAS)

AF:

0.357

AC:

14142

AN:

39614

South Asian (SAS)

AF:

0.0223

AC:

1922

AN:

86010

European-Finnish (FIN)

AF:

0.00331

AC:

175

AN:

52822

Middle Eastern (MID)

AF:

0.0171

AC:

AN:

5318

European-Non Finnish (NFE)

AF:

0.00280

AC:

3109

AN:

1111794

Other (OTH)

AF:

0.0441

AC:

2661

AN:

60286

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

1421

2841

4262

5682

7103

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

558

1116

1674

2232

2790

<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:

0.0839

AC:

12771

AN:

152206

Hom.:

1361

Cov.:

AF XY:

0.0871

AC XY:

6479

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.186

AC:

7725

AN:

41506

American (AMR)

AF:

0.154

AC:

2353

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00836

AC:

AN:

3468

East Asian (EAS)

AF:

0.402

AC:

2076

AN:

5164

South Asian (SAS)

AF:

0.0320

AC:

154

AN:

4820

European-Finnish (FIN)

AF:

0.00358

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00363

AC:

247

AN:

68016

Other (OTH)

AF:

0.0695

AC:

147

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

527

1055

1582

2110

2637

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

256

384

512

640

<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:

0.0278

Hom.:

416

Bravo

AF:

0.101

Asia WGS

AF:

0.176

AC:

611

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Congenital stationary night blindness autosomal dominant 1 (1)

Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

9.9

(source)

DANN

Benign

0.80

PhyloP100

1.4

PromoterAI

-0.024

Neutral

(source)

Mutation Taster

=300/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over