3-129533079-A-T

Variant names:

• chr3-129533079-A-T
• rs2855557
• NM_000539.3:c.936+307A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000539.3(RHO):​c.936+307A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 152,038 control chromosomes in the GnomAD database, including 17,322 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.37 (17322 hom., cov: 32)
• Consequence: RHO NM_000539.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.113
• Publications: 10 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHO	NM_000539.3	c.936+307A>T		intron_variant	Intron 4 of 4	ENST00000296271.4	NP_000530.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHO	ENST00000296271.4	c.936+307A>T		intron_variant	Intron 4 of 4	1	NM_000539.3	ENSP00000296271.3

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56868 AN: 151918 Hom.: 17261 Cov.: 32

Gnomad AFR AF: 0.814

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.0704

Gnomad MID AF: 0.279

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.342

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.375 AC: 56990 AN: 152038 Hom.: 17322 Cov.: 32 AF XY: 0.375 AC XY: 27859 AN XY: 74310

African (AFR) AF: 0.815 AC: 33757 AN: 41442

American (AMR) AF: 0.342 AC: 5230 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 996 AN: 3470

East Asian (EAS) AF: 0.632 AC: 3259 AN: 5154

South Asian (SAS) AF: 0.378 AC: 1823 AN: 4822

European-Finnish (FIN) AF: 0.0704 AC: 746 AN: 10596

Middle Eastern (MID) AF: 0.266 AC: 77 AN: 290

European-Non Finnish (NFE) AF: 0.150 AC: 10222 AN: 67978

Other (OTH) AF: 0.342 AC: 717 AN: 2098

Alfa AF: 0.247 Hom.: 1092

Bravo AF: 0.412

Asia WGS AF: 0.499 AC: 1738 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.64
DANN	Benign	0.49
PhyloP100		-0.11
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: rs2855557; hg19: chr3-129251922;