Genetic Variant NM_001142800.2:c.863-23_863-22dupTT (chr6-65405388-G-GAA) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2 link	c.863-23_863-22dupTT	intron_variant	Intron 5 of 42	ENST00000503581.6	NP_001136272.1	Q5T1H1-1
EYS	NM_001292009.2 link	c.863-23_863-22dupTT	intron_variant	Intron 5 of 43		NP_001278938.1	Q5T1H1-3
EYS	NM_001142801.2 link	c.863-23_863-22dupTT	intron_variant	Intron 5 of 11		NP_001136273.1	Q5T1H1-4
EYS	NM_198283.2 link	c.863-23_863-22dupTT	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_863-21insTT	intron_variant	Intron 5 of 42	5	NM_001142800.2	ENSP00000424243.1	Q5T1H1-1
EYS	ENST00000370621.7 link	c.863-22_863-21insTT	intron_variant	Intron 5 of 43	1		ENSP00000359655.3	Q5T1H1-3
EYS	ENST00000393380.6 link	c.863-22_863-21insTT	intron_variant	Intron 5 of 11	1		ENSP00000377042.2	Q5T1H1-4
EYS	ENST00000342421.9 link	c.863-22_863-21insTT	intron_variant	Intron 3 of 8	1		ENSP00000341818.5	Q5T1H1-2

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

GnomAD3 exomes

AF:

0.234

AC:

47327

AN:

202572

Hom.:

3128

AF XY:

0.234

AC XY:

25940

AN XY:

110630

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 SAS exome

AF:

0.292

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

Gnomad4 AFR exome

AF:

0.229

Gnomad4 AMR exome

AF:

0.260

Gnomad4 ASJ exome

AF:

0.203

Gnomad4 EAS exome

AF:

0.246

Gnomad4 SAS exome

AF:

0.298

Gnomad4 FIN exome

AF:

0.229

Gnomad4 NFE exome

AF:

0.195

Gnomad4 OTH exome

AF:

0.207

GnomAD4 genome

AF:

0.231

AC:

34244

AN:

148126

Hom.:

4035

Cov.:

AF XY:

0.237

AC XY:

17066

AN XY:

72104

show subpopulations

Gnomad4 AFR

AF:

0.257

Gnomad4 AMR

AF:

0.213

Gnomad4 ASJ

AF:

0.232

Gnomad4 EAS

AF:

0.277

Gnomad4 SAS

AF:

0.351

Gnomad4 FIN

AF:

0.249

Gnomad4 NFE

AF:

0.208

Gnomad4 OTH

AF:

0.220

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

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over