Variant chr3-129532420-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

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=-0.9).

BP6

Variant 3-129532420-C-T is Benign according to our data. Variant chr3-129532420-C-T is described in ClinVar as [Benign]. Clinvar id is 256384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-129532420-C-T is described in Lovd as [Benign]. Variant chr3-129532420-C-T is described in Lovd as [Likely_benign].

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/exons	MANE	Protein	UniProt
RHO	NM_000539.3 linkuse as main transcript	c.696+4C>T		splice_region_variant, intron_variant		ENST00000296271.4	NP_000530.1	P08100

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHO	ENST00000296271.4 linkuse as main transcript	c.696+4C>T		splice_region_variant, intron_variant		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

GnomAD3 exomes

AF:

0.0815

AC:

20448

AN:

250880

Hom.:

947

AF XY:

0.0854

AC XY:

11593

AN XY:

135682

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 SAS exome

AF:

0.115

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

Gnomad4 AFR exome

AF:

0.0691

Gnomad4 AMR exome

AF:

0.0621

Gnomad4 ASJ exome

AF:

0.163

Gnomad4 EAS exome

AF:

0.0510

Gnomad4 SAS exome

AF:

0.118

Gnomad4 FIN exome

AF:

0.0379

Gnomad4 NFE exome

AF:

0.0853

Gnomad4 OTH exome

AF:

0.0935

GnomAD4 genome

AF:

0.0781

AC:

11874

AN:

152106

Hom.:

525

Cov.:

AF XY:

0.0776

AC XY:

5770

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0700

Gnomad4 AMR

AF:

0.0801

Gnomad4 ASJ

AF:

0.161

Gnomad4 EAS

AF:

0.0635

Gnomad4 SAS

AF:

0.108

Gnomad4 FIN

AF:

0.0374

Gnomad4 NFE

AF:

0.0836

Gnomad4 OTH

AF:

0.0956

Alfa

AF:

0.0859

Hom.:

314

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Pigmentary retinal dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Retinitis pigmentosa 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Congenital stationary night blindness autosomal dominant 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.0020

DANN

Benign

0.64

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over