Genetic Variant EYS:c.6424+40255C>A (chr6-64190337-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001142800.2(EYS):c.6424+40255C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0271 in 152,244 control chromosomes in the GnomAD database, including 59 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 0.027 ( 59 hom., cov: 32)

Consequence

EYS
NM_001142800.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.178

Publications

1 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0271 (4124/152244) while in subpopulation AFR AF = 0.0425 (1764/41542). AF 95% confidence interval is 0.0408. There are 59 homozygotes in GnomAd4. There are 1984 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 59 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2 link	c.6424+40255C>A		intron_variant	Intron 31 of 42	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2 link	c.6424+40255C>A		intron_variant	Intron 31 of 43		NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6 link	c.6424+40255C>A		intron_variant	Intron 31 of 42	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7 link	c.6424+40255C>A		intron_variant	Intron 31 of 43	1		ENSP00000359655.3

Frequencies

GnomAD3 genomes

AF:

0.0271

AC:

4128

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0427

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.0184

Gnomad ASJ

AF:

0.00462

Gnomad EAS

AF:

0.0349

Gnomad SAS

AF:

0.0348

Gnomad FIN

AF:

0.00999

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0228

Gnomad OTH

AF:

0.0168

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

GnomAD4 genome

AF:

0.0271

AC:

4124

AN:

152244

Hom.:

Cov.:

AF XY:

0.0266

AC XY:

1984

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.0425

AC:

1764

AN:

41542

American (AMR)

AF:

0.0184

AC:

281

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00462

AC:

AN:

3466

East Asian (EAS)

AF:

0.0348

AC:

180

AN:

5178

South Asian (SAS)

AF:

0.0350

AC:

169

AN:

4828

European-Finnish (FIN)

AF:

0.00999

AC:

106

AN:

10614

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0228

AC:

1548

AN:

68008

Other (OTH)

AF:

0.0166

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

206

413

619

826

1032

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<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:

0.0263

Hom.:

Bravo

AF:

0.0277

Asia WGS

AF:

0.0250

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.0

(source)

DANN

Benign

0.51

PhyloP100

-0.18

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over