dbSNP rs34154043: EYS:c.863-22delT (chr6-65405388-GA-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001142800.2(EYS):c.863-22delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00297 in 1,485,430 control chromosomes in the GnomAD database, including 27 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0023 ( 3 hom., cov: 0)

Exomes 𝑓: 0.0030 ( 24 hom. )

Consequence

EYS
NM_001142800.2 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.391

Publications

4 publications found

Variant links:

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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine

EYS links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAd4 at 3 AR,AD gene

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EYS	NM_001142800.2	MANE Select	c.863-22delT	intron	N/A	NP_001136272.1	Q5T1H1-1
EYS	NM_001292009.2		c.863-22delT	intron	N/A	NP_001278938.1	Q5T1H1-3
EYS	NM_001142801.2		c.863-22delT	intron	N/A	NP_001136273.1	Q5T1H1-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EYS	ENST00000503581.6	TSL:5 MANE Select	c.863-22delT	intron	N/A	ENSP00000424243.1	Q5T1H1-1
EYS	ENST00000370621.7	TSL:1	c.863-22delT	intron	N/A	ENSP00000359655.3	Q5T1H1-3
EYS	ENST00000393380.6	TSL:1	c.863-22delT	intron	N/A	ENSP00000377042.2	Q5T1H1-4

Frequencies

GnomAD3 genomes

AF:

0.00233

AC:

345

AN:

148276

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000570

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00552

Gnomad ASJ

AF:

0.000290

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000211

Gnomad FIN

AF:

0.000420

Gnomad MID

AF:

0.00641

Gnomad NFE

AF:

0.00337

Gnomad OTH

AF:

0.00294

GnomAD2 exomes

AF:

0.00246

AC:

499

AN:

202572

AF XY:

0.00256

show subpopulations

Gnomad AFR exome

AF:

0.000808

Gnomad AMR exome

AF:

0.00401

Gnomad ASJ exome

AF:

0.00125

Gnomad EAS exome

AF:

0.0000692

Gnomad FIN exome

AF:

0.000325

Gnomad NFE exome

AF:

0.00340

Gnomad OTH exome

AF:

0.00403

GnomAD4 exome

AF:

0.00304

AC:

4064

AN:

1337052

Hom.:

Cov.:

AF XY:

0.00305

AC XY:

2039

AN XY:

669014

show subpopulations

African (AFR)

AF:

0.000499

AC:

AN:

30070

American (AMR)

AF:

0.00363

AC:

139

AN:

38294

Ashkenazi Jewish (ASJ)

AF:

0.00103

AC:

AN:

24172

East Asian (EAS)

AF:

0.0000791

AC:

AN:

37924

South Asian (SAS)

AF:

0.00109

AC:

AN:

76992

European-Finnish (FIN)

AF:

0.000505

AC:

AN:

51438

Middle Eastern (MID)

AF:

0.00281

AC:

AN:

5340

European-Non Finnish (NFE)

AF:

0.00352

AC:

3578

AN:

1017254

Other (OTH)

AF:

0.00322

AC:

179

AN:

55568

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

Heterozygous variant carriers

183

367

550

734

917

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

264

396

528

660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00233

AC:

345

AN:

148378

Hom.:

Cov.:

AF XY:

0.00251

AC XY:

181

AN XY:

72244

show subpopulations

African (AFR)

AF:

0.000568

AC:

AN:

40502

American (AMR)

AF:

0.00551

AC:

AN:

14886

Ashkenazi Jewish (ASJ)

AF:

0.000290

AC:

AN:

3448

East Asian (EAS)

AF:

0.00

AC:

AN:

5040

South Asian (SAS)

AF:

0.000212

AC:

AN:

4726

European-Finnish (FIN)

AF:

0.000420

AC:

AN:

9528

Middle Eastern (MID)

AF:

0.00690

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00337

AC:

226

AN:

66996

Other (OTH)

AF:

0.00291

AC:

AN:

2060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.526

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00204

Hom.:

270

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.39

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over