chr6-63885181-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001142800.2(EYS):​c.7056-20823A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 151,956 control chromosomes in the GnomAD database, including 20,624 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 0.50 ( 20624 hom., cov: 32)

Consequence

EYS
NM_001142800.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.599

Publications

2 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

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=-0.89).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EYSNM_001142800.2 linkc.7056-20823A>G intron_variant Intron 35 of 42 ENST00000503581.6 NP_001136272.1 Q5T1H1-1
EYSNM_001292009.2 linkc.7056-20823A>G intron_variant Intron 35 of 43 NP_001278938.1 Q5T1H1-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EYSENST00000503581.6 linkc.7056-20823A>G intron_variant Intron 35 of 42 5 NM_001142800.2 ENSP00000424243.1 Q5T1H1-1
EYSENST00000370621.7 linkc.7056-20823A>G intron_variant Intron 35 of 43 1 ENSP00000359655.3 Q5T1H1-3
EYSENST00000398580.3 linkc.369-20823A>G intron_variant Intron 3 of 9 5 ENSP00000381585.3 H0Y3Q4

Frequencies

GnomAD3 genomes
AF:
0.502
AC:
76179
AN:
151838
Hom.:
20579
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.696
Gnomad AMI
AF:
0.377
Gnomad AMR
AF:
0.536
Gnomad ASJ
AF:
0.476
Gnomad EAS
AF:
0.460
Gnomad SAS
AF:
0.538
Gnomad FIN
AF:
0.332
Gnomad MID
AF:
0.452
Gnomad NFE
AF:
0.407
Gnomad OTH
AF:
0.462
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.502
AC:
76281
AN:
151956
Hom.:
20624
Cov.:
32
AF XY:
0.502
AC XY:
37277
AN XY:
74286
show subpopulations
African (AFR)
AF:
0.696
AC:
28878
AN:
41466
American (AMR)
AF:
0.536
AC:
8185
AN:
15258
Ashkenazi Jewish (ASJ)
AF:
0.476
AC:
1649
AN:
3464
East Asian (EAS)
AF:
0.460
AC:
2377
AN:
5168
South Asian (SAS)
AF:
0.539
AC:
2595
AN:
4812
European-Finnish (FIN)
AF:
0.332
AC:
3507
AN:
10548
Middle Eastern (MID)
AF:
0.459
AC:
134
AN:
292
European-Non Finnish (NFE)
AF:
0.407
AC:
27651
AN:
67936
Other (OTH)
AF:
0.458
AC:
962
AN:
2102
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
1799
3597
5396
7194
8993
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
650
1300
1950
2600
3250
<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:
0.443
Hom.:
9558
Bravo
AF:
0.525
Asia WGS
AF:
0.469
AC:
1631
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
0.29
DANN
Benign
0.40
PhyloP100
-0.60
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs729291; hg19: chr6-64595074; API