rs321498

Positions:

• chr6-63869331-T-C
• chr6-63869331-T-G

Variant summary

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

The NM_001142800.2(EYS):​c.7056-4973A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 151,908 control chromosomes in the GnomAD database, including 28,562 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 0.60 (28562 hom., cov: 31)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EYS	NM_001142800.2	c.7056-4973A>G		intron_variant		ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.7056-4973A>G		intron_variant			NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.7056-4973A>G		intron_variant		5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.7056-4973A>G		intron_variant		1		ENSP00000359655.3
EYS	ENST00000398580.3	c.369-4973A>G		intron_variant		5		ENSP00000381585.3

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91514 AN: 151790 Hom.: 28558 Cov.: 31

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.706

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.673

Gnomad OTH AF: 0.612

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

GnomAD4 genome AF: 0.603 AC: 91546 AN: 151908 Hom.: 28562 Cov.: 31 AF XY: 0.604 AC XY: 44824 AN XY: 74232

Gnomad4 AFR AF: 0.451

Gnomad4 AMR AF: 0.577

Gnomad4 ASJ AF: 0.580

Gnomad4 EAS AF: 0.707

Gnomad4 SAS AF: 0.527

Gnomad4 FIN AF: 0.765

Gnomad4 NFE AF: 0.673

Gnomad4 OTH AF: 0.615

Alfa AF: 0.646 Hom.: 31037

Bravo AF: 0.584

Asia WGS AF: 0.629 AC: 2187 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.7
DANN	Benign	0.36

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: rs321498; hg19: chr6-64579224; COSMIC: COSV65482168;