NM_001142800.2:c.5644+23375C>T

Variant names:

• chr6-64566848-G-A
• rs587592
• NM_001142800.2:c.5644+23375C>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.5644+23375C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 152,054 control chromosomes in the GnomAD database, including 44,697 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 0.76 (44697 hom., cov: 31)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.370
• 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.5644+23375C>T		intron_variant	Intron 26 of 42	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.5644+23375C>T		intron_variant	Intron 26 of 43		NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.5644+23375C>T		intron_variant	Intron 26 of 42	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.5644+23375C>T		intron_variant	Intron 26 of 43	1		ENSP00000359655.3

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115457 AN: 151936 Hom.: 44637 Cov.: 31

Gnomad AFR AF: 0.918

Gnomad AMI AF: 0.657

Gnomad AMR AF: 0.744

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.776

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.707

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

GnomAD4 genome AF: 0.760 AC: 115573 AN: 152054 Hom.: 44697 Cov.: 31 AF XY: 0.759 AC XY: 56406 AN XY: 74310

African (AFR) AF: 0.918 AC: 38106 AN: 41520

American (AMR) AF: 0.744 AC: 11343 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.651 AC: 2258 AN: 3470

East Asian (EAS) AF: 0.663 AC: 3416 AN: 5152

South Asian (SAS) AF: 0.775 AC: 3733 AN: 4814

European-Finnish (FIN) AF: 0.702 AC: 7417 AN: 10570

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.692 AC: 47025 AN: 67968

Other (OTH) AF: 0.710 AC: 1496 AN: 2106

Alfa AF: 0.728 Hom.: 5005

Bravo AF: 0.768

Asia WGS AF: 0.745 AC: 2588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.39
DANN	Benign	0.21
PhyloP100		-0.37
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: rs587592; hg19: chr6-65276741;