rs2071093

Variant names:

• chr3-129533761-C-A
• rs2071093
• NM_000539.3:c.*43C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-129533761-C-A
• chr3-129533761-C-T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_000539.3(RHO):​c.*43C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0855 in 1,333,446 control chromosomes in the GnomAD database, including 5,324 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.078 (512 hom., cov: 32)
  • Exomes 𝑓: 0.086 (4812 hom.)
• Consequence: RHO NM_000539.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.175
• Publications: 6 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: Labcorp Genetics (formerly Invitae), G2P
• inherited retinal dystrophy

  Inheritance: SD, AD Classification: DEFINITIVE Submitted by: ClinGen
• retinitis pigmentosa 4

  Inheritance: SD, AR, AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 3-129533761-C-A is Benign according to our data. Variant chr3-129533761-C-A is described in ClinVar as Benign. ClinVar VariationId is 256382.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0994 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHO	NM_000539.3	MANE Select	c.*43C>A		3_prime_UTR	Exon 5 of 5	NP_000530.1	P08100

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHO	ENST00000296271.4	TSL:1 MANE Select	c.*43C>A		3_prime_UTR	Exon 5 of 5	ENSP00000296271.3	P08100

Frequencies

GnomAD3 genomes AF: 0.0775 AC: 11786 AN: 152130 Hom.: 511 Cov.: 32

Gnomad AFR AF: 0.0686

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0770

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.0631

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.0382

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0839

Gnomad OTH AF: 0.0951

GnomAD2 exomes AF: 0.0813 AC: 20150 AN: 247754 AF XY: 0.0854

Gnomad AFR exome AF: 0.0709

Gnomad AMR exome AF: 0.0562

Gnomad ASJ exome AF: 0.163

Gnomad EAS exome AF: 0.0632

Gnomad FIN exome AF: 0.0367

Gnomad NFE exome AF: 0.0842

Gnomad OTH exome AF: 0.0997

GnomAD4 exome AF: 0.0865 AC: 102165 AN: 1181198 Hom.: 4812 Cov.: 17 AF XY: 0.0885 AC XY: 53245 AN XY: 601450

African (AFR) AF: 0.0701 AC: 1962 AN: 27980

American (AMR) AF: 0.0582 AC: 2583 AN: 44346

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 4024 AN: 24512

East Asian (EAS) AF: 0.0491 AC: 1883 AN: 38340

South Asian (SAS) AF: 0.118 AC: 9519 AN: 80704

European-Finnish (FIN) AF: 0.0382 AC: 1977 AN: 51736

Middle Eastern (MID) AF: 0.130 AC: 661 AN: 5074

European-Non Finnish (NFE) AF: 0.0871 AC: 74714 AN: 857312

Other (OTH) AF: 0.0946 AC: 4842 AN: 51194

GnomAD4 genome AF: 0.0775 AC: 11800 AN: 152248 Hom.: 512 Cov.: 32 AF XY: 0.0771 AC XY: 5738 AN XY: 74440

African (AFR) AF: 0.0687 AC: 2856 AN: 41544

American (AMR) AF: 0.0769 AC: 1176 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 558 AN: 3468

East Asian (EAS) AF: 0.0627 AC: 325 AN: 5182

South Asian (SAS) AF: 0.107 AC: 516 AN: 4822

European-Finnish (FIN) AF: 0.0382 AC: 405 AN: 10616

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0839 AC: 5706 AN: 68002

Other (OTH) AF: 0.0960 AC: 203 AN: 2114

Alfa AF: 0.0701 Hom.: 223

Bravo AF: 0.0797

Asia WGS AF: 0.106 AC: 371 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Congenital stationary night blindness autosomal dominant 1 (1)
-	-	1	not specified (1)
-	-	1	Pigmentary retinal dystrophy (1)
-	-	1	Retinitis pigmentosa (1)
-	-	1	Retinitis pigmentosa 4 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	3.0
DANN	Benign	0.68
PhyloP100		0.17
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: rs2071093; hg19: chr3-129252604;