rs9351470

Positions:

• chr6-64939881-G-A
• chr6-64939881-G-C

Variant summary

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

The NM_001142800.2(EYS):​c.2381+5912C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.823 in 151,922 control chromosomes in the GnomAD database, including 52,060 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 0.82 (52060 hom., cov: 31)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EYS	NM_001142800.2	c.2381+5912C>T		intron_variant		ENST00000503581.6
EYS	NM_001292009.2	c.2381+5912C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EYS	ENST00000503581.6	c.2381+5912C>T		intron_variant		5	NM_001142800.2	A2
EYS	ENST00000370621.7	c.2381+5912C>T		intron_variant		1		P2

Frequencies

GnomAD3 genomes AF: 0.823 AC: 124902 AN: 151802 Hom.: 52015 Cov.: 31

Gnomad AFR AF: 0.946

Gnomad AMI AF: 0.876

Gnomad AMR AF: 0.812

Gnomad ASJ AF: 0.846

Gnomad EAS AF: 0.575

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.662

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.799

Gnomad OTH AF: 0.826

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

GnomAD4 genome AF: 0.823 AC: 125005 AN: 151922 Hom.: 52060 Cov.: 31 AF XY: 0.814 AC XY: 60450 AN XY: 74220

Gnomad4 AFR AF: 0.946

Gnomad4 AMR AF: 0.812

Gnomad4 ASJ AF: 0.846

Gnomad4 EAS AF: 0.574

Gnomad4 SAS AF: 0.715

Gnomad4 FIN AF: 0.662

Gnomad4 NFE AF: 0.799

Gnomad4 OTH AF: 0.827

Alfa AF: 0.807 Hom.: 73636

Bravo AF: 0.837

Asia WGS AF: 0.711 AC: 2472 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.10
DANN	Benign	0.24

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: rs9351470; hg19: chr6-65649774;