chr3-129528683-G-A

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

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

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 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
RHONM_000539.3 linkuse as main transcriptc.-51G>A 5_prime_UTR_variant 1/5 ENST00000296271.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RHOENST00000296271.4 linkuse as main transcriptc.-51G>A 5_prime_UTR_variant 1/51 NM_000539.3 P1

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
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.:
31
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.:
33
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:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMar 03, 2015- -
Congenital stationary night blindness autosomal dominant 1 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This 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 submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This 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

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