rs3003672

Positions:

• chr6-64121227-A-C
• chr6-64121227-A-G

Variant summary

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

The NM_001142800.2(EYS):​c.6425-39225T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0831 in 152,224 control chromosomes in the GnomAD database, including 1,375 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 0.083 (1375 hom., cov: 32)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.205

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EYS	NM_001142800.2	c.6425-39225T>G		intron_variant		ENST00000503581.6
EYS	NM_001292009.2	c.6425-39225T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EYS	ENST00000503581.6	c.6425-39225T>G		intron_variant		5	NM_001142800.2	A2
EYS	ENST00000370621.7	c.6425-39225T>G		intron_variant		1		P2

Frequencies

GnomAD3 genomes AF: 0.0830 AC: 12630 AN: 152106 Hom.: 1374 Cov.: 32

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0481

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.0791

Gnomad SAS AF: 0.0153

Gnomad FIN AF: 0.0463

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00322

Gnomad OTH AF: 0.0612

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

GnomAD4 genome AF: 0.0831 AC: 12653 AN: 152224 Hom.: 1375 Cov.: 32 AF XY: 0.0824 AC XY: 6136 AN XY: 74432

Gnomad4 AFR AF: 0.255

Gnomad4 AMR AF: 0.0483

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.0787

Gnomad4 SAS AF: 0.0151

Gnomad4 FIN AF: 0.0463

Gnomad4 NFE AF: 0.00322

Gnomad4 OTH AF: 0.0616

Alfa AF: 0.0125 Hom.: 163

Bravo AF: 0.0924

Asia WGS AF: 0.0590 AC: 203 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.91
DANN	Benign	0.32

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: rs3003672; hg19: chr6-64831120;