chr6-65405388-G-GAAA

Variant names:

Variant summary

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

The NM_001142800.2(EYS):c.863-24_863-22dupTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 1,465,574 control chromosomes in the GnomAD database, including 19,769 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.20 ( 3752 hom., cov: 0)

Exomes 𝑓: 0.23 ( 16017 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), 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-GAAA is Benign according to our data. Variant chr6-65405388-G-GAAA is described in CliVar as Benign. Clinvar id is 1294289.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-65405388-G-GAAA is described in CliVar as Benign. Clinvar id is 1294289.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-65405388-G-GAAA is described in CliVar as Benign. Clinvar id is 1294289.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-65405388-G-GAAA is described in CliVar as Benign. Clinvar id is 1294289.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-65405388-G-GAAA is described in CliVar as Benign. Clinvar id is 1294289.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-65405388-G-GAAA is described in CliVar as Benign. Clinvar id is 1294289.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-65405388-G-GAAA is described in CliVar as Benign. Clinvar id is 1294289.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-65405388-G-GAAA is described in CliVar as Benign. Clinvar id is 1294289.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2 link	c.863-24_863-22dupTTT	intron_variant	Intron 5 of 42	ENST00000503581.6	NP_001136272.1	Q5T1H1-1
EYS	NM_001292009.2 link	c.863-24_863-22dupTTT	intron_variant	Intron 5 of 43		NP_001278938.1	Q5T1H1-3
EYS	NM_001142801.2 link	c.863-24_863-22dupTTT	intron_variant	Intron 5 of 11		NP_001136273.1	Q5T1H1-4
EYS	NM_198283.2 link	c.863-24_863-22dupTTT	intron_variant	Intron 4 of 9		NP_938024.1	Q5T1H1-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
EYS	ENST00000503581.6 link	c.863-22_863-21insTTT	intron_variant	Intron 5 of 42	5	NM_001142800.2	ENSP00000424243.1	Q5T1H1-1
EYS	ENST00000370621.7 link	c.863-22_863-21insTTT	intron_variant	Intron 5 of 43	1		ENSP00000359655.3	Q5T1H1-3
EYS	ENST00000393380.6 link	c.863-22_863-21insTTT	intron_variant	Intron 5 of 11	1		ENSP00000377042.2	Q5T1H1-4
EYS	ENST00000342421.9 link	c.863-22_863-21insTTT	intron_variant	Intron 3 of 8	1		ENSP00000341818.5	Q5T1H1-2

Frequencies

GnomAD3 genomes

AF:

0.205

AC:

30311

AN:

148014

Hom.:

3750

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0616

Gnomad AMI

AF:

0.514

Gnomad AMR

AF:

0.265

Gnomad ASJ

AF:

0.238

Gnomad EAS

AF:

0.188

Gnomad SAS

AF:

0.150

Gnomad FIN

AF:

0.268

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.267

Gnomad OTH

AF:

0.237

GnomAD2 exomes

AF:

0.204

AC:

41232

AN:

202572

AF XY:

0.204

show subpopulations

Gnomad AFR exome

AF:

0.0530

Gnomad AMR exome

AF:

0.214

Gnomad ASJ exome

AF:

0.225

Gnomad EAS exome

AF:

0.170

Gnomad FIN exome

AF:

0.242

Gnomad NFE exome

AF:

0.231

Gnomad OTH exome

AF:

0.219

GnomAD4 exome

AF:

0.226

AC:

298144

AN:

1317460

Hom.:

16017

Cov.:

AF XY:

0.225

AC XY:

148108

AN XY:

658590

show subpopulations

African (AFR)

AF:

0.0575

AC:

1709

AN:

29730

American (AMR)

AF:

0.214

AC:

8008

AN:

37466

Ashkenazi Jewish (ASJ)

AF:

0.224

AC:

5321

AN:

23730

East Asian (EAS)

AF:

0.171

AC:

6348

AN:

37016

South Asian (SAS)

AF:

0.148

AC:

11103

AN:

74894

European-Finnish (FIN)

AF:

0.247

AC:

12333

AN:

50012

Middle Eastern (MID)

AF:

0.219

AC:

1158

AN:

5292

European-Non Finnish (NFE)

AF:

0.239

AC:

240371

AN:

1004556

Other (OTH)

AF:

0.215

AC:

11793

AN:

54764

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

9124

18248

27373

36497

45621

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8556

17112

25668

34224

42780

<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:

0.205

AC:

30314

AN:

148114

Hom.:

3752

Cov.:

AF XY:

0.205

AC XY:

14812

AN XY:

72100

show subpopulations

African (AFR)

AF:

0.0615

AC:

2489

AN:

40474

American (AMR)

AF:

0.264

AC:

3925

AN:

14844

Ashkenazi Jewish (ASJ)

AF:

0.238

AC:

819

AN:

3442

East Asian (EAS)

AF:

0.189

AC:

950

AN:

5036

South Asian (SAS)

AF:

0.151

AC:

711

AN:

4718

European-Finnish (FIN)

AF:

0.268

AC:

2534

AN:

9446

Middle Eastern (MID)

AF:

0.255

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.267

AC:

17863

AN:

66904

Other (OTH)

AF:

0.236

AC:

485

AN:

2058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

979

1958

2937

3916

4895

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

324

648

972

1296

1620

<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:

0.158

Hom.:

270

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 11, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Retinitis pigmentosa 25

Benign:1

Sep 27, 2019

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over