rs2410

Variant names:

• chr3-129533950-A-G
• rs2410
• NM_000539.3:c.*232A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-129533950-A-G
• chr3-129533950-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000539.3(RHO):​c.*232A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0941 in 497,922 control chromosomes in the GnomAD database, including 7,903 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (3249 hom., cov: 32)
  • Exomes 𝑓: 0.077 (4654 hom.)
• Consequence: RHO NM_000539.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.780
• Publications: 8 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 3-129533950-A-G is Benign according to our data. Variant chr3-129533950-A-G is described in ClinVar as Benign. ClinVar VariationId is 343290.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.533 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHO	NM_000539.3	MANE Select	c.*232A>G		3_prime_UTR	Exon 5 of 5	NP_000530.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHO	ENST00000296271.4	TSL:1 MANE Select	c.*232A>G		3_prime_UTR	Exon 5 of 5	ENSP00000296271.3

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20015 AN: 151520 Hom.: 3239 Cov.: 32

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.00866

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.0103

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.00614

Gnomad OTH AF: 0.104

GnomAD4 exome AF: 0.0773 AC: 26775 AN: 346286 Hom.: 4654 Cov.: 0 AF XY: 0.0797 AC XY: 14470 AN XY: 181548

African (AFR) AF: 0.313 AC: 3267 AN: 10442

American (AMR) AF: 0.161 AC: 2311 AN: 14352

Ashkenazi Jewish (ASJ) AF: 0.00815 AC: 89 AN: 10916

East Asian (EAS) AF: 0.528 AC: 12581 AN: 23846

South Asian (SAS) AF: 0.143 AC: 5534 AN: 38784

European-Finnish (FIN) AF: 0.00916 AC: 177 AN: 19318

Middle Eastern (MID) AF: 0.0201 AC: 31 AN: 1544

European-Non Finnish (NFE) AF: 0.00634 AC: 1313 AN: 206978

Other (OTH) AF: 0.0732 AC: 1472 AN: 20106

GnomAD4 genome AF: 0.132 AC: 20065 AN: 151636 Hom.: 3249 Cov.: 32 AF XY: 0.137 AC XY: 10163 AN XY: 74094

African (AFR) AF: 0.318 AC: 13130 AN: 41312

American (AMR) AF: 0.169 AC: 2575 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.00866 AC: 30 AN: 3466

East Asian (EAS) AF: 0.550 AC: 2827 AN: 5138

South Asian (SAS) AF: 0.159 AC: 755 AN: 4748

European-Finnish (FIN) AF: 0.0103 AC: 108 AN: 10524

Middle Eastern (MID) AF: 0.0137 AC: 4 AN: 292

European-Non Finnish (NFE) AF: 0.00614 AC: 417 AN: 67898

Other (OTH) AF: 0.104 AC: 219 AN: 2112

Alfa AF: 0.0658 Hom.: 734

Bravo AF: 0.152

Asia WGS AF: 0.315 AC: 1095 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.9
DANN	Benign	0.57
PhyloP100		0.78
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs2410; hg19: chr3-129252793; COSMIC: COSV56215006;