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.

• 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, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, ClinGen

ACMG classification

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RS1	NM_000330.4	c.52+4364G>A		intron_variant	Intron 1 of 5	ENST00000379984.4	NP_000321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RS1	ENST00000379984.4	c.52+4364G>A		intron_variant	Intron 1 of 5	1	NM_000330.4	ENSP00000369320.3

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 v4.3

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

Other links and lift over

dbSNP: rs62589000; hg19: chrX-18685773;