rs9353441

Variant names:

• chr6-64021122-A-G
• rs9353441
• NM_001142800.2:c.6726-21939T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142800.2(EYS):​c.6726-21939T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 151,732 control chromosomes in the GnomAD database, including 7,759 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 0.32 (7759 hom., cov: 31)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.195

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]

LOC107986608 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.6726-21939T>C		intron_variant	Intron 33 of 42	ENST00000503581.6	NP_001136272.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.6726-21939T>C		intron_variant	Intron 33 of 42	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.6726-21939T>C		intron_variant	Intron 33 of 43	1		ENSP00000359655.3
EYS	ENST00000398580.3	c.39-21939T>C		intron_variant	Intron 1 of 9	5		ENSP00000381585.3

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47941 AN: 151616 Hom.: 7757 Cov.: 31

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.316 AC: 47962 AN: 151732 Hom.: 7759 Cov.: 31 AF XY: 0.312 AC XY: 23125 AN XY: 74142

Gnomad4 AFR AF: 0.289

Gnomad4 AMR AF: 0.269

Gnomad4 ASJ AF: 0.357

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.309

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.341

Alfa AF: 0.335 Hom.: 4276

Bravo AF: 0.316

Asia WGS AF: 0.261 AC: 909 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.2
DANN	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs9353441; hg19: chr6-64731015;