rs4509103

chr6-64190337-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001142800.2(EYS):c.6424+40255C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0271 in 152,244 control chromosomes in the GnomAD database, including 59 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 0.027 (59 hom., cov: 32)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.178

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=-0.9).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0271 (4124/152244) while in subpopulation AFR AF= 0.0425 (1764/41542). AF 95% confidence interval is 0.0408. There are 59 homozygotes in gnomad4. There are 1984 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 59 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EYS	NM_001142800.2	c.6424+40255C>A		intron_variant		ENST00000503581.6
EYS	NM_001292009.2	c.6424+40255C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EYS	ENST00000503581.6	c.6424+40255C>A		intron_variant		5	NM_001142800.2	A2
EYS	ENST00000370621.7	c.6424+40255C>A		intron_variant		1		P2

Frequencies

GnomAD3 genomes AF: 0.0271 AC: 4128 AN: 152126 Hom.: 59 Cov.: 32

Gnomad AFR AF: 0.0427

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0184

Gnomad ASJ AF: 0.00462

Gnomad EAS AF: 0.0349

Gnomad SAS AF: 0.0348

Gnomad FIN AF: 0.00999

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0228

Gnomad OTH AF: 0.0168

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

GnomAD4 genome AF: 0.0271 AC: 4124 AN: 152244 Hom.: 59 Cov.: 32 AF XY: 0.0266 AC XY: 1984 AN XY: 74450

Gnomad4 AFR AF: 0.0425

Gnomad4 AMR AF: 0.0184

Gnomad4 ASJ AF: 0.00462

Gnomad4 EAS AF: 0.0348

Gnomad4 SAS AF: 0.0350

Gnomad4 FIN AF: 0.00999

Gnomad4 NFE AF: 0.0228

Gnomad4 OTH AF: 0.0166

Alfa AF: 0.0257 Hom.: 7

Bravo AF: 0.0277

Asia WGS AF: 0.0250 AC: 87 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.0
Dann	Benign	0.51

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: rs4509103; hg19: chr6-64900230;