rs1041522

Positions:

• chr6-65119497-C-T

Variant summary

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

The NM_001142800.2(EYS):​c.2024-61770G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 151,744 control chromosomes in the GnomAD database, including 23,018 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 0.54 (23018 hom., cov: 30)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.582

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EYS	NM_001142800.2	c.2024-61770G>A		intron_variant		ENST00000503581.6
EYS	NM_001292009.2	c.2024-61770G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EYS	ENST00000503581.6	c.2024-61770G>A		intron_variant		5	NM_001142800.2	A2
EYS	ENST00000370621.7	c.2024-61770G>A		intron_variant		1		P2

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82039 AN: 151626 Hom.: 22982 Cov.: 30

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.523

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

GnomAD4 genome AF: 0.541 AC: 82131 AN: 151744 Hom.: 23018 Cov.: 30 AF XY: 0.539 AC XY: 39913 AN XY: 74116

Gnomad4 AFR AF: 0.658

Gnomad4 AMR AF: 0.449

Gnomad4 ASJ AF: 0.502

Gnomad4 EAS AF: 0.175

Gnomad4 SAS AF: 0.456

Gnomad4 FIN AF: 0.581

Gnomad4 NFE AF: 0.522

Gnomad4 OTH AF: 0.522

Alfa AF: 0.520 Hom.: 42306

Bravo AF: 0.532

Asia WGS AF: 0.345 AC: 1204 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.13
DANN	Benign	0.15

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: rs1041522; hg19: chr6-65829390;