chr6-64500697-C-T

Variant names:

• chr6-64500697-C-T
• rs16895338
• NM_001142800.2:c.5645-61345G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000503581.6(EYS):​c.5645-61345G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 151,882 control chromosomes in the GnomAD database, including 5,472 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 0.25 (5472 hom., cov: 32)
• Consequence: EYS ENST00000503581.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.882
• Publications: 1 publications found

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]

EYS Gene-Disease associations (from GenCC):

• EYS-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• retinitis pigmentosa

  Inheritance: AR, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
• retinitis pigmentosa 25

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -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 = 0.341 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000503581.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	NM_001142800.2	MANE Select	c.5645-61345G>A		intron	N/A	NP_001136272.1
	EYS	NM_001292009.2		c.5645-61345G>A		intron	N/A	NP_001278938.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	ENST00000503581.6	TSL:5 MANE Select	c.5645-61345G>A		intron	N/A	ENSP00000424243.1
	EYS	ENST00000370621.7	TSL:1	c.5645-61345G>A		intron	N/A	ENSP00000359655.3

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38432 AN: 151766 Hom.: 5475 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.355

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.282

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

GnomAD4 genome AF: 0.253 AC: 38429 AN: 151882 Hom.: 5472 Cov.: 32 AF XY: 0.255 AC XY: 18907 AN XY: 74214

African (AFR) AF: 0.105 AC: 4364 AN: 41480

American (AMR) AF: 0.267 AC: 4079 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1158 AN: 3464

East Asian (EAS) AF: 0.355 AC: 1828 AN: 5150

South Asian (SAS) AF: 0.257 AC: 1234 AN: 4802

European-Finnish (FIN) AF: 0.349 AC: 3680 AN: 10538

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 21001 AN: 67878

Other (OTH) AF: 0.280 AC: 589 AN: 2106

Alfa AF: 0.285 Hom.: 4288

Bravo AF: 0.246

Asia WGS AF: 0.283 AC: 981 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.0
DANN	Benign	0.56
PhyloP100		0.88
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16895338; hg19: chr6-65210590;