chr6-65503753-G-A

Variant names:

• chr6-65503753-G-A
• rs4710292
• NM_001142800.2:c.-332-7760C>T

Variant summary

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

The NM_001142800.2(EYS):​c.-332-7760C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 151,334 control chromosomes in the GnomAD database, including 19,623 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 (19623 hom., cov: 32)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79
• 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=-1.11).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.-332-7760C>T		intron_variant	Intron 2 of 42	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.-332-7760C>T		intron_variant	Intron 2 of 43		NP_001278938.1
EYS	NM_001142801.2	c.-332-7760C>T		intron_variant	Intron 2 of 11		NP_001136273.1
EYS	NM_198283.2	c.-332-7760C>T		intron_variant	Intron 1 of 9		NP_938024.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.-332-7760C>T		intron_variant	Intron 2 of 42	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.-332-7760C>T		intron_variant	Intron 2 of 43	1		ENSP00000359655.3
EYS	ENST00000393380.6	c.-332-7760C>T		intron_variant	Intron 2 of 11	1		ENSP00000377042.2
EYS	ENST00000489873.1	n.196-7760C>T		intron_variant	Intron 2 of 4	1

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75524 AN: 151216 Hom.: 19584 Cov.: 32

Gnomad AFR AF: 0.620

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.553

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

GnomAD4 genome AF: 0.500 AC: 75624 AN: 151334 Hom.: 19623 Cov.: 32 AF XY: 0.501 AC XY: 37072 AN XY: 73982

African (AFR) AF: 0.620 AC: 25650 AN: 41370

American (AMR) AF: 0.598 AC: 9060 AN: 15160

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1834 AN: 3456

East Asian (EAS) AF: 0.500 AC: 2579 AN: 5162

South Asian (SAS) AF: 0.477 AC: 2296 AN: 4814

European-Finnish (FIN) AF: 0.386 AC: 4065 AN: 10542

Middle Eastern (MID) AF: 0.575 AC: 168 AN: 292

European-Non Finnish (NFE) AF: 0.421 AC: 28412 AN: 67528

Other (OTH) AF: 0.551 AC: 1158 AN: 2100

Alfa AF: 0.481 Hom.: 2568

Bravo AF: 0.519

Asia WGS AF: 0.502 AC: 1742 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.34
DANN	Benign	0.18
PhyloP100		-1.8
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: rs4710292; hg19: chr6-66213646;