rs62589000

Variant names:

• chrX-18667653-C-T
• rs62589000
• NM_000330.4:c.52+4364G>A

Variant summary

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

The NM_000330.4(RS1):​c.52+4364G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 110,179 control chromosomes in the GnomAD database, including 2,124 homozygotes. There are 7,315 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. The gene RS1 is included in the ClinGen Criteria Specification Registry.

• Frequency: Genomes: 𝑓 0.21 (2124 hom., 7315 hem., cov: 22)
• Consequence: RS1 NM_000330.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610
• Publications: 6 publications found

Genes affected

RS1 (HGNC:10457): (retinoschisin 1) This gene encodes an extracellular protein that plays a crucial role in the cellular organization of the retina. The encoded protein is assembled and secreted from photoreceptors and bipolar cells as a homo-oligomeric protein complex. Mutations in this gene are responsible for X-linked retinoschisis, a common, early-onset macular degeneration in males that results in a splitting of the inner layers of the retina and severe loss in vision. [provided by RefSeq, Oct 2008]

RS1 Gene-Disease associations (from GenCC):

• retinoschisis

  Inheritance: XL Classification: DEFINITIVE Submitted by: G2P
• X-linked retinoschisis

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Myriad Women's Health, PanelApp Australia, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Specifications for RS1 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000330.4. 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
	RS1	NM_000330.4	MANE Select	c.52+4364G>A		intron	N/A	NP_000321.1	O15537

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RS1	ENST00000379984.4	TSL:1 MANE Select	c.52+4364G>A		intron	N/A	ENSP00000369320.3	O15537

Frequencies

GnomAD3 genomes AF: 0.214 AC: 23558 AN: 110145 Hom.: 2122 Cov.: 22

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.0869

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.242

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

GnomAD4 genome AF: 0.214 AC: 23576 AN: 110179 Hom.: 2124 Cov.: 22 AF XY: 0.225 AC XY: 7315 AN XY: 32475

African (AFR) AF: 0.160 AC: 4847 AN: 30338

American (AMR) AF: 0.424 AC: 4367 AN: 10289

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 614 AN: 2627

East Asian (EAS) AF: 0.576 AC: 1993 AN: 3463

South Asian (SAS) AF: 0.330 AC: 840 AN: 2542

European-Finnish (FIN) AF: 0.222 AC: 1267 AN: 5719

Middle Eastern (MID) AF: 0.181 AC: 39 AN: 215

European-Non Finnish (NFE) AF: 0.174 AC: 9178 AN: 52805

Other (OTH) AF: 0.248 AC: 372 AN: 1502

Alfa AF: 0.182 Hom.: 1056

Bravo AF: 0.237

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.1
DANN	Benign	0.64
PhyloP100		0.061
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs62589000;

hg19: chrX-18685773;