chr3-129533950-A-G

Variant names:

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

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Congenital stationary night blindness autosomal dominant 1 (1)
-	-	1	not provided (1)
-	-	1	Retinitis pigmentosa (1)

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;