6-63869914-C-T

Variant names:

• chr6-63869914-C-T
• rs321494
• NM_001142800.2:c.7056-5556G>A

Variant summary

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

The NM_001142800.2(EYS):​c.7056-5556G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 151,828 control chromosomes in the GnomAD database, including 19,815 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 0.49 (19815 hom., cov: 31)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.12
• Publications: 2 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.7056-5556G>A		intron_variant	Intron 35 of 42	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.7056-5556G>A		intron_variant	Intron 35 of 43		NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.7056-5556G>A		intron_variant	Intron 35 of 42	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.7056-5556G>A		intron_variant	Intron 35 of 43	1		ENSP00000359655.3
EYS	ENST00000398580.3	c.369-5556G>A		intron_variant	Intron 3 of 9	5		ENSP00000381585.3

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73772 AN: 151710 Hom.: 19815 Cov.: 31

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.623

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.539

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.669

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.527

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

GnomAD4 genome AF: 0.486 AC: 73775 AN: 151828 Hom.: 19815 Cov.: 31 AF XY: 0.487 AC XY: 36112 AN XY: 74210

African (AFR) AF: 0.256 AC: 10607 AN: 41392

American (AMR) AF: 0.465 AC: 7081 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1814 AN: 3468

East Asian (EAS) AF: 0.539 AC: 2778 AN: 5154

South Asian (SAS) AF: 0.460 AC: 2216 AN: 4818

European-Finnish (FIN) AF: 0.669 AC: 7068 AN: 10568

Middle Eastern (MID) AF: 0.541 AC: 158 AN: 292

European-Non Finnish (NFE) AF: 0.595 AC: 40366 AN: 67896

Other (OTH) AF: 0.531 AC: 1120 AN: 2108

Alfa AF: 0.523 Hom.: 6933

Bravo AF: 0.461

Asia WGS AF: 0.524 AC: 1821 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.15
DANN	Benign	0.19
PhyloP100		-2.1
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: rs321494; hg19: chr6-64579807;