chr6-64021122-A-G

Variant names:

• chr6-64021122-A-G
• rs9353441
• NM_001142800.2:c.6726-21939T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142800.2(EYS):​c.6726-21939T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 151,732 control chromosomes in the GnomAD database, including 7,759 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 0.32 (7759 hom., cov: 31)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.195
• Publications: 5 publications found

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

LOC107986608 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.6726-21939T>C		intron_variant	Intron 33 of 42	ENST00000503581.6	NP_001136272.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.6726-21939T>C		intron_variant	Intron 33 of 42	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.6726-21939T>C		intron_variant	Intron 33 of 43	1		ENSP00000359655.3
EYS	ENST00000398580.3	c.39-21939T>C		intron_variant	Intron 1 of 9	5		ENSP00000381585.3

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47941 AN: 151616 Hom.: 7757 Cov.: 31

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.316 AC: 47962 AN: 151732 Hom.: 7759 Cov.: 31 AF XY: 0.312 AC XY: 23125 AN XY: 74142

African (AFR) AF: 0.289 AC: 11942 AN: 41366

American (AMR) AF: 0.269 AC: 4101 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 1238 AN: 3466

East Asian (EAS) AF: 0.269 AC: 1391 AN: 5162

South Asian (SAS) AF: 0.309 AC: 1485 AN: 4804

European-Finnish (FIN) AF: 0.285 AC: 2980 AN: 10466

Middle Eastern (MID) AF: 0.384 AC: 112 AN: 292

European-Non Finnish (NFE) AF: 0.345 AC: 23462 AN: 67908

Other (OTH) AF: 0.341 AC: 718 AN: 2108

Alfa AF: 0.335 Hom.: 4734

Bravo AF: 0.316

Asia WGS AF: 0.261 AC: 909 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.2
DANN	Benign	0.74
PhyloP100		0.20
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

Other links and lift over

dbSNP: rs9353441; hg19: chr6-64731015;