chr6-64823173-C-T

Variant names:

• chr6-64823173-C-T
• rs10498828
• NM_001142800.2:c.2993-351G>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.2993-351G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 151,464 control chromosomes in the GnomAD database, including 2,114 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 0.17 (2114 hom., cov: 32)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• Publications: 9 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142800.2. 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.2993-351G>A		intron	N/A	NP_001136272.1
	EYS	NM_001292009.2		c.2993-351G>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.2993-351G>A		intron	N/A	ENSP00000424243.1
	EYS	ENST00000370621.7	TSL:1	c.2993-351G>A		intron	N/A	ENSP00000359655.3

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25098 AN: 151348 Hom.: 2113 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.166 AC: 25115 AN: 151464 Hom.: 2114 Cov.: 32 AF XY: 0.164 AC XY: 12126 AN XY: 73984

African (AFR) AF: 0.146 AC: 6038 AN: 41356

American (AMR) AF: 0.150 AC: 2273 AN: 15166

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 713 AN: 3462

East Asian (EAS) AF: 0.123 AC: 628 AN: 5114

South Asian (SAS) AF: 0.178 AC: 857 AN: 4814

European-Finnish (FIN) AF: 0.138 AC: 1454 AN: 10518

Middle Eastern (MID) AF: 0.182 AC: 53 AN: 292

European-Non Finnish (NFE) AF: 0.186 AC: 12609 AN: 67730

Other (OTH) AF: 0.156 AC: 328 AN: 2102

Alfa AF: 0.181 Hom.: 1220

Bravo AF: 0.167

Asia WGS AF: 0.146 AC: 509 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.33
DANN	Benign	0.72
PhyloP100		-1.6
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: rs10498828; hg19: chr6-65533066;