6-63794359-A-G

Variant names:

• chr6-63794359-A-G
• rs319920
• NM_001142800.2:c.7412-5135T>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.7412-5135T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 152,056 control chromosomes in the GnomAD database, including 22,008 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 0.51 (22008 hom., cov: 32)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.77
• Publications: 2 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.7412-5135T>C		intron_variant	Intron 37 of 42	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.7412-5135T>C		intron_variant	Intron 37 of 43		NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.7412-5135T>C		intron_variant	Intron 37 of 42	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.7412-5135T>C		intron_variant	Intron 37 of 43	1		ENSP00000359655.3
EYS	ENST00000398580.3	c.725-5135T>C		intron_variant	Intron 5 of 9	5		ENSP00000381585.3
EYS	ENST00000486069.1	n.52-5135T>C		intron_variant	Intron 1 of 5	3

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77963 AN: 151938 Hom.: 21958 Cov.: 32

Gnomad AFR AF: 0.749

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.474

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

GnomAD4 genome AF: 0.513 AC: 78071 AN: 152056 Hom.: 22008 Cov.: 32 AF XY: 0.513 AC XY: 38100 AN XY: 74314

African (AFR) AF: 0.749 AC: 31062 AN: 41474

American (AMR) AF: 0.536 AC: 8180 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.461 AC: 1598 AN: 3466

East Asian (EAS) AF: 0.461 AC: 2382 AN: 5166

South Asian (SAS) AF: 0.535 AC: 2578 AN: 4822

European-Finnish (FIN) AF: 0.330 AC: 3486 AN: 10568

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.401 AC: 27274 AN: 67972

Other (OTH) AF: 0.470 AC: 991 AN: 2110

Alfa AF: 0.448 Hom.: 10694

Bravo AF: 0.539

Asia WGS AF: 0.471 AC: 1637 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.21
DANN	Benign	0.51
PhyloP100		-4.8
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: rs319920; hg19: chr6-64504252;