rs12205984

Positions:

• chr6-63862726-A-G
• chr6-63862726-A-T

Variant summary

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

The NM_001142800.2(EYS):​c.7228+1460T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 152,122 control chromosomes in the GnomAD database, including 20,199 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 0.50 (20199 hom., cov: 32)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.279

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).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EYS	NM_001142800.2	c.7228+1460T>C		intron_variant		ENST00000503581.6
EYS	NM_001292009.2	c.7228+1460T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EYS	ENST00000503581.6	c.7228+1460T>C		intron_variant		5	NM_001142800.2	A2
EYS	ENST00000370621.7	c.7228+1460T>C		intron_variant		1		P2
EYS	ENST00000398580.3	c.542+1460T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75514 AN: 152004 Hom.: 20152 Cov.: 32

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.455

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

GnomAD4 genome AF: 0.497 AC: 75617 AN: 152122 Hom.: 20199 Cov.: 32 AF XY: 0.497 AC XY: 36982 AN XY: 74376

Gnomad4 AFR AF: 0.687

Gnomad4 AMR AF: 0.527

Gnomad4 ASJ AF: 0.477

Gnomad4 EAS AF: 0.459

Gnomad4 SAS AF: 0.540

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.404

Gnomad4 OTH AF: 0.451

Alfa AF: 0.455 Hom.: 4821

Bravo AF: 0.520

Asia WGS AF: 0.464 AC: 1612 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.1
DANN	Benign	0.73

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: rs12205984; hg19: chr6-64572619;