NM_001142800.2:c.5644+26621A>G

Variant names:

• chr6-64563602-T-C
• rs16880108
• NM_001142800.2:c.5644+26621A>G

Variant summary

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

The NM_001142800.2(EYS):​c.5644+26621A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,022 control chromosomes in the GnomAD database, including 4,169 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 0.22 (4169 hom., cov: 32)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.101
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.323 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.5644+26621A>G		intron	N/A	NP_001136272.1
	EYS	NM_001292009.2		c.5644+26621A>G		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.5644+26621A>G		intron	N/A	ENSP00000424243.1
	EYS	ENST00000370621.7	TSL:1	c.5644+26621A>G		intron	N/A	ENSP00000359655.3

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33462 AN: 151904 Hom.: 4164 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.237

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

GnomAD4 genome AF: 0.220 AC: 33478 AN: 152022 Hom.: 4169 Cov.: 32 AF XY: 0.224 AC XY: 16639 AN XY: 74300

African (AFR) AF: 0.104 AC: 4335 AN: 41540

American (AMR) AF: 0.331 AC: 5043 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1126 AN: 3470

East Asian (EAS) AF: 0.292 AC: 1508 AN: 5168

South Asian (SAS) AF: 0.288 AC: 1393 AN: 4832

European-Finnish (FIN) AF: 0.251 AC: 2651 AN: 10560

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.246 AC: 16693 AN: 67880

Other (OTH) AF: 0.243 AC: 513 AN: 2110

Alfa AF: 0.239 Hom.: 2387

Bravo AF: 0.221

Asia WGS AF: 0.306 AC: 1061 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.3
DANN	Benign	0.80
PhyloP100		0.10
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: rs16880108; hg19: chr6-65273495;