rs12208631

chr6-64341636-A-G

Variant summary

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

The NM_001142800.2(EYS):c.6079-34554T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0277 in 151,790 control chromosomes in the GnomAD database, including 88 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 0.028 (88 hom., cov: 32)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240

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=-0.91).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0277 (4200/151790) while in subpopulation NFE AF= 0.0407 (2757/67748). AF 95% confidence interval is 0.0394. There are 88 homozygotes in gnomad4. There are 1994 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 87 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EYS	NM_001142800.2	c.6079-34554T>C		intron_variant		ENST00000503581.6
EYS	NM_001292009.2	c.6079-34554T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EYS	ENST00000503581.6	c.6079-34554T>C		intron_variant		5	NM_001142800.2	A2
EYS	ENST00000370621.7	c.6079-34554T>C		intron_variant		1		P2

Frequencies

GnomAD3 genomes AF: 0.0277 AC: 4199 AN: 151672 Hom.: 87 Cov.: 32

Gnomad AFR AF: 0.00705

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0232

Gnomad ASJ AF: 0.0916

Gnomad EAS AF: 0.000195

Gnomad SAS AF: 0.0226

Gnomad FIN AF: 0.0260

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0407

Gnomad OTH AF: 0.0400

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

GnomAD4 genome AF: 0.0277 AC: 4200 AN: 151790 Hom.: 88 Cov.: 32 AF XY: 0.0269 AC XY: 1994 AN XY: 74174

Gnomad4 AFR AF: 0.00703

Gnomad4 AMR AF: 0.0232

Gnomad4 ASJ AF: 0.0916

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.0228

Gnomad4 FIN AF: 0.0260

Gnomad4 NFE AF: 0.0407

Gnomad4 OTH AF: 0.0396

Alfa AF: 0.0336 Hom.: 13

Bravo AF: 0.0264

Asia WGS AF: 0.0110 AC: 37 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.3
Dann	Benign	0.63

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: rs12208631; hg19: chr6-65051529;