3-129528683-G-A

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

2

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]

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 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 rank MANE Protein UniProt
RHONM_000539.3 linkc.-51G>A 5_prime_UTR_variant Exon 1 of 5 ENST00000296271.4 NP_000530.1 P08100

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RHOENST00000296271 linkc.-51G>A 5_prime_UTR_variant Exon 1 of 5 1 NM_000539.3 ENSP00000296271.3 P08100

Frequencies

GnomAD3 genomes
AF:
0.0837
AC:
12729
AN:
152088
Hom.:
1359
Cov.:
33
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.:
31
AF XY:
0.0229
AC XY:
16630
AN XY:
726300
show subpopulations
Gnomad4 AFR exome
AF:
0.184
AC:
6140
AN:
33396
Gnomad4 AMR exome
AF:
0.160
AC:
7129
AN:
44592
Gnomad4 ASJ exome
AF:
0.00632
AC:
165
AN:
26120
Gnomad4 EAS exome
AF:
0.357
AC:
14142
AN:
39614
Gnomad4 SAS exome
AF:
0.0223
AC:
1922
AN:
86010
Gnomad4 FIN exome
AF:
0.00331
AC:
175
AN:
52822
Gnomad4 NFE exome
AF:
0.00280
AC:
3109
AN:
1111794
Gnomad4 Remaining exome
AF:
0.0441
AC:
2661
AN:
60286
Heterozygous variant carriers
0
1421
2841
4262
5682
7103
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
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.:
33
AF XY:
0.0871
AC XY:
6479
AN XY:
74418
show subpopulations
Gnomad4 AFR
AF:
0.186
AC:
0.186118
AN:
0.186118
Gnomad4 AMR
AF:
0.154
AC:
0.153891
AN:
0.153891
Gnomad4 ASJ
AF:
0.00836
AC:
0.00836217
AN:
0.00836217
Gnomad4 EAS
AF:
0.402
AC:
0.402014
AN:
0.402014
Gnomad4 SAS
AF:
0.0320
AC:
0.0319502
AN:
0.0319502
Gnomad4 FIN
AF:
0.00358
AC:
0.00357748
AN:
0.00357748
Gnomad4 NFE
AF:
0.00363
AC:
0.0036315
AN:
0.0036315
Gnomad4 OTH
AF:
0.0695
AC:
0.0695364
AN:
0.0695364
Heterozygous variant carriers
0
527
1055
1582
2110
2637
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
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

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
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

- -

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

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. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.64
CADD
Benign
9.9
DANN
Benign
0.80
Mutation Taster
=300/0
polymorphism (auto)

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.

Other links and lift over

dbSNP: rs2269736; hg19: chr3-129247526; COSMIC: COSV56213998; API