rs16896407

Positions:

• chr6-65218936-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.2023+76927C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0184 in 152,006 control chromosomes in the GnomAD database, including 102 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 0.018 (102 hom., cov: 32)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.137

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]

LOC107986607 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EYS	NM_001142800.2	c.2023+76927C>G		intron_variant		ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.2023+76927C>G		intron_variant			NP_001278938.1
LOC107986607	XR_001744187.1	n.223-329C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.2023+76927C>G		intron_variant		5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.2023+76927C>G		intron_variant		1		ENSP00000359655.3

Frequencies

GnomAD3 genomes AF: 0.0184 AC: 2792 AN: 151888 Hom.: 101 Cov.: 32

Gnomad AFR AF: 0.00334

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0510

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.0160

Gnomad FIN AF: 0.0621

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00556

Gnomad OTH AF: 0.0245

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

GnomAD4 genome AF: 0.0184 AC: 2802 AN: 152006 Hom.: 102 Cov.: 32 AF XY: 0.0217 AC XY: 1611 AN XY: 74300

Gnomad4 AFR AF: 0.00333

Gnomad4 AMR AF: 0.0512

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.0160

Gnomad4 FIN AF: 0.0621

Gnomad4 NFE AF: 0.00557

Gnomad4 OTH AF: 0.0271

Alfa AF: 0.0128 Hom.: 3

Bravo AF: 0.0200

Asia WGS AF: 0.0910 AC: 314 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.6
DANN	Benign	0.85

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: rs16896407; hg19: chr6-65928829;