rs756274

Positions:

• chr6-63795320-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.7412-6096T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 152,074 control chromosomes in the GnomAD database, including 12,267 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 0.39 (12267 hom., cov: 32)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.496

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EYS	NM_001142800.2	c.7412-6096T>C		intron_variant		ENST00000503581.6
EYS	NM_001292009.2	c.7412-6096T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EYS	ENST00000503581.6	c.7412-6096T>C		intron_variant		5	NM_001142800.2	A2
EYS	ENST00000370621.7	c.7412-6096T>C		intron_variant		1		P2
EYS	ENST00000398580.3	c.726-6096T>C		intron_variant		5
EYS	ENST00000486069.1	n.52-6096T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59588 AN: 151956 Hom.: 12251 Cov.: 32

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.392 AC: 59628 AN: 152074 Hom.: 12267 Cov.: 32 AF XY: 0.387 AC XY: 28787 AN XY: 74332

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.422

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.284

Gnomad4 SAS AF: 0.361

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.385

Alfa AF: 0.369 Hom.: 14433

Bravo AF: 0.413

Asia WGS AF: 0.307 AC: 1066 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	1.4
DANN	Benign	0.66

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: rs756274; hg19: chr6-64505213;