6-64568231-A-G

Variant names:

• chr6-64568231-A-G
• rs17403480
• NM_001142800.2:c.5644+21992T>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.5644+21992T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0979 in 152,192 control chromosomes in the GnomAD database, including 871 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 0.098 (871 hom., cov: 32)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100
• Publications: 1 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.5644+21992T>C		intron_variant	Intron 26 of 42	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.5644+21992T>C		intron_variant	Intron 26 of 43		NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.5644+21992T>C		intron_variant	Intron 26 of 42	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.5644+21992T>C		intron_variant	Intron 26 of 43	1		ENSP00000359655.3

Frequencies

GnomAD3 genomes AF: 0.0980 AC: 14904 AN: 152074 Hom.: 872 Cov.: 32

Gnomad AFR AF: 0.0442

Gnomad AMI AF: 0.0242

Gnomad AMR AF: 0.0591

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.0202

Gnomad SAS AF: 0.0911

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.0785

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

GnomAD4 genome AF: 0.0979 AC: 14893 AN: 152192 Hom.: 871 Cov.: 32 AF XY: 0.0982 AC XY: 7302 AN XY: 74386

African (AFR) AF: 0.0440 AC: 1830 AN: 41550

American (AMR) AF: 0.0589 AC: 901 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 366 AN: 3468

East Asian (EAS) AF: 0.0203 AC: 105 AN: 5182

South Asian (SAS) AF: 0.0903 AC: 435 AN: 4816

European-Finnish (FIN) AF: 0.180 AC: 1904 AN: 10562

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9148 AN: 68004

Other (OTH) AF: 0.0781 AC: 165 AN: 2112

Alfa AF: 0.113 Hom.: 1821

Bravo AF: 0.0855

Asia WGS AF: 0.0530 AC: 184 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.73
DANN	Benign	0.58
PhyloP100		0.0010
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: rs17403480; hg19: chr6-65278124;