3-129528708-A-G

Variant names:

• chr3-129528708-A-G
• rs7984
• NM_000539.3:c.-26A>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.-26A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,613,362 control chromosomes in the GnomAD database, including 61,563 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (17743 hom., cov: 32)
  • Exomes 𝑓: 0.20 (43820 hom.)
• Consequence: RHO NM_000539.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -1.33
• Publications: 20 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 3-129528708-A-G is Benign according to our data. Variant chr3-129528708-A-G is described in ClinVar as Benign. ClinVar VariationId is 256383.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.819 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.-26A>G		5_prime_UTR	Exon 1 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.-26A>G		5_prime_UTR	Exon 1 of 5	ENSP00000296271.3	P08100

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57383 AN: 151928 Hom.: 17682 Cov.: 32

Gnomad AFR AF: 0.826

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.0702

Gnomad MID AF: 0.287

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.344

GnomAD2 exomes AF: 0.277 AC: 69244 AN: 250244 AF XY: 0.268

Gnomad AFR exome AF: 0.838

Gnomad AMR exome AF: 0.277

Gnomad ASJ exome AF: 0.276

Gnomad EAS exome AF: 0.637

Gnomad FIN exome AF: 0.0668

Gnomad NFE exome AF: 0.153

Gnomad OTH exome AF: 0.243

GnomAD4 exome AF: 0.200 AC: 291721 AN: 1461316 Hom.: 43820 Cov.: 33 AF XY: 0.204 AC XY: 148025 AN XY: 726934

African (AFR) AF: 0.853 AC: 28533 AN: 33458

American (AMR) AF: 0.281 AC: 12539 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 7290 AN: 26134

East Asian (EAS) AF: 0.589 AC: 23357 AN: 39684

South Asian (SAS) AF: 0.379 AC: 32696 AN: 86218

European-Finnish (FIN) AF: 0.0703 AC: 3747 AN: 53304

Middle Eastern (MID) AF: 0.301 AC: 1709 AN: 5676

European-Non Finnish (NFE) AF: 0.150 AC: 166486 AN: 1111804

Other (OTH) AF: 0.255 AC: 15364 AN: 60360

GnomAD4 genome AF: 0.378 AC: 57507 AN: 152046 Hom.: 17743 Cov.: 32 AF XY: 0.378 AC XY: 28116 AN XY: 74330

African (AFR) AF: 0.826 AC: 34264 AN: 41468

American (AMR) AF: 0.342 AC: 5229 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 991 AN: 3468

East Asian (EAS) AF: 0.632 AC: 3254 AN: 5146

South Asian (SAS) AF: 0.383 AC: 1840 AN: 4810

European-Finnish (FIN) AF: 0.0702 AC: 744 AN: 10600

Middle Eastern (MID) AF: 0.274 AC: 80 AN: 292

European-Non Finnish (NFE) AF: 0.150 AC: 10215 AN: 67976

Other (OTH) AF: 0.345 AC: 727 AN: 2106

Alfa AF: 0.431 Hom.: 6541

Bravo AF: 0.417

Asia WGS AF: 0.505 AC: 1760 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	1	Congenital stationary night blindness autosomal dominant 1 (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	-0.90
CADD	Benign	0.56
DANN	Benign	0.29
PhyloP100		-1.3
PromoterAI		0.0094	Neutral
Mutation Taster		=300/0	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: rs7984; hg19: chr3-129247551; COSMIC: COSV56214291;