Genetic Variant EYS:c.863-23_863-22dupTT (chr6-65405388-G-GAA) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001142800.2(EYS):c.863-23_863-22dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 1,469,002 control chromosomes in the GnomAD database, including 20,765 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.23 ( 4035 hom., cov: 0)

Exomes 𝑓: 0.21 ( 16730 hom. )

Consequence

EYS
NM_001142800.2 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:2

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: Benign. The variant received -10 ACMG points.

BP6

Variant 6-65405388-G-GAA is Benign according to our data. Variant chr6-65405388-G-GAA is described in ClinVar as Benign. ClinVar VariationId is 1225094.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.337 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EYS	NM_001142800.2	MANE Select	c.863-23_863-22dupTT	intron	N/A	NP_001136272.1	Q5T1H1-1
EYS	NM_001292009.2		c.863-23_863-22dupTT	intron	N/A	NP_001278938.1	Q5T1H1-3
EYS	NM_001142801.2		c.863-23_863-22dupTT	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.863-22_863-21insTT	intron	N/A	ENSP00000424243.1	Q5T1H1-1
EYS	ENST00000370621.7	TSL:1	c.863-22_863-21insTT	intron	N/A	ENSP00000359655.3	Q5T1H1-3
EYS	ENST00000393380.6	TSL:1	c.863-22_863-21insTT	intron	N/A	ENSP00000377042.2	Q5T1H1-4

Frequencies

GnomAD3 genomes

AF:

0.231

AC:

34198

AN:

148036

Hom.:

4024

Cov.:

show subpopulations

Gnomad AFR

AF:

0.256

Gnomad AMI

AF:

0.103

Gnomad AMR

AF:

0.212

Gnomad ASJ

AF:

0.232

Gnomad EAS

AF:

0.278

Gnomad SAS

AF:

0.352

Gnomad FIN

AF:

0.249

Gnomad MID

AF:

0.179

Gnomad NFE

AF:

0.208

Gnomad OTH

AF:

0.220

GnomAD2 exomes

AF:

0.234

AC:

47327

AN:

202572

AF XY:

0.234

show subpopulations

Gnomad AFR exome

AF:

0.242

Gnomad AMR exome

AF:

0.273

Gnomad ASJ exome

AF:

0.209

Gnomad EAS exome

AF:

0.260

Gnomad FIN exome

AF:

0.235

Gnomad NFE exome

AF:

0.205

Gnomad OTH exome

AF:

0.226

GnomAD4 exome

AF:

0.207

AC:

273176

AN:

1320876

Hom.:

16730

Cov.:

AF XY:

0.209

AC XY:

138299

AN XY:

660614

show subpopulations

African (AFR)

AF:

0.229

AC:

6828

AN:

29876

American (AMR)

AF:

0.260

AC:

9783

AN:

37656

Ashkenazi Jewish (ASJ)

AF:

0.203

AC:

4846

AN:

23856

East Asian (EAS)

AF:

0.246

AC:

9247

AN:

37542

South Asian (SAS)

AF:

0.298

AC:

22626

AN:

75966

European-Finnish (FIN)

AF:

0.229

AC:

11560

AN:

50470

Middle Eastern (MID)

AF:

0.182

AC:

967

AN:

5302

European-Non Finnish (NFE)

AF:

0.195

AC:

195969

AN:

1005262

Other (OTH)

AF:

0.207

AC:

11350

AN:

54946

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

9037

18074

27110

36147

45184

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7160

14320

21480

28640

35800

<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:

0.231

AC:

34244

AN:

148126

Hom.:

4035

Cov.:

AF XY:

0.237

AC XY:

17066

AN XY:

72104

show subpopulations

African (AFR)

AF:

0.257

AC:

10386

AN:

40432

American (AMR)

AF:

0.213

AC:

3161

AN:

14850

Ashkenazi Jewish (ASJ)

AF:

0.232

AC:

801

AN:

3446

East Asian (EAS)

AF:

0.277

AC:

1396

AN:

5032

South Asian (SAS)

AF:

0.351

AC:

1656

AN:

4714

European-Finnish (FIN)

AF:

0.249

AC:

2356

AN:

9478

Middle Eastern (MID)

AF:

0.162

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.208

AC:

13894

AN:

66924

Other (OTH)

AF:

0.220

AC:

454

AN:

2060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

1213

2426

3640

4853

6066

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

366

732

1098

1464

1830

<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:

0.160

Hom.:

270

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Retinitis pigmentosa 25 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.39

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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