rs9453276

Variant names:

• chr6-65362933-A-G
• rs9453276
• NM_001142800.2:c.1300-9316T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-65362933-A-G
• chr6-65362933-A-T

Variant summary

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

The NM_001142800.2(EYS):​c.1300-9316T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 151,936 control chromosomes in the GnomAD database, including 34,602 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 0.67 (34602 hom., cov: 32)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167
• Publications: 3 publications found

Genes affected

EYS (HGNC:21555): (eyes shut homolog) The product of this gene contains multiple epidermal growth factor (EGF)-like and LamG domains. The protein is expressed in the photoreceptor layer of the retina, and the gene is mutated in autosomal recessive retinitis pigmentosa. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

EYS Gene-Disease associations (from GenCC):

• EYS-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• retinitis pigmentosa

  Inheritance: AR, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
• retinitis pigmentosa 25

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.1300-9316T>C		intron_variant	Intron 8 of 42	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.1300-9316T>C		intron_variant	Intron 8 of 43		NP_001278938.1
EYS	NM_001142801.2	c.1300-9316T>C		intron_variant	Intron 8 of 11		NP_001136273.1
EYS	NM_198283.2	c.1300-9316T>C		intron_variant	Intron 7 of 9		NP_938024.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.1300-9316T>C		intron_variant	Intron 8 of 42	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.1300-9316T>C		intron_variant	Intron 8 of 43	1		ENSP00000359655.3
EYS	ENST00000393380.6	c.1300-9316T>C		intron_variant	Intron 8 of 11	1		ENSP00000377042.2
EYS	ENST00000342421.9	c.1300-9316T>C		intron_variant	Intron 6 of 8	1		ENSP00000341818.5

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102334 AN: 151818 Hom.: 34589 Cov.: 32

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.704

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.711

Gnomad FIN AF: 0.682

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.646

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

GnomAD4 genome AF: 0.674 AC: 102389 AN: 151936 Hom.: 34602 Cov.: 32 AF XY: 0.672 AC XY: 49889 AN XY: 74248

African (AFR) AF: 0.689 AC: 28571 AN: 41476

American (AMR) AF: 0.608 AC: 9268 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.704 AC: 2442 AN: 3470

East Asian (EAS) AF: 0.599 AC: 3082 AN: 5144

South Asian (SAS) AF: 0.711 AC: 3428 AN: 4818

European-Finnish (FIN) AF: 0.682 AC: 7200 AN: 10562

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.684 AC: 46427 AN: 67920

Other (OTH) AF: 0.647 AC: 1364 AN: 2108

Alfa AF: 0.680 Hom.: 6104

Bravo AF: 0.668

Asia WGS AF: 0.645 AC: 2237 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.9
DANN	Benign	0.79
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: rs9453276; hg19: chr6-66072826;