6-64357689-A-G

Variant names:

• chr6-64357689-A-G
• rs626316
• NM_001142800.2:c.6078+31001T>C

Variant summary

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

The NM_001292009.2(EYS):​c.6078+31001T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.753 in 151,406 control chromosomes in the GnomAD database, including 43,585 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 0.75 (43585 hom., cov: 32)
• Consequence: EYS NM_001292009.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.849
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001292009.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	NM_001142800.2	MANE Select	c.6078+31001T>C		intron	N/A	NP_001136272.1
	EYS	NM_001292009.2		c.6078+31001T>C		intron	N/A	NP_001278938.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	ENST00000503581.6	TSL:5 MANE Select	c.6078+31001T>C		intron	N/A	ENSP00000424243.1
	EYS	ENST00000370621.7	TSL:1	c.6078+31001T>C		intron	N/A	ENSP00000359655.3

Frequencies

GnomAD3 genomes AF: 0.753 AC: 113953 AN: 151288 Hom.: 43530 Cov.: 32

Gnomad AFR AF: 0.893

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.722

Gnomad ASJ AF: 0.726

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.727

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.711

Gnomad OTH AF: 0.725

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

GnomAD4 genome AF: 0.753 AC: 114067 AN: 151406 Hom.: 43585 Cov.: 32 AF XY: 0.750 AC XY: 55458 AN XY: 73968

African (AFR) AF: 0.893 AC: 36986 AN: 41422

American (AMR) AF: 0.721 AC: 10924 AN: 15144

Ashkenazi Jewish (ASJ) AF: 0.726 AC: 2510 AN: 3456

East Asian (EAS) AF: 0.566 AC: 2880 AN: 5090

South Asian (SAS) AF: 0.727 AC: 3497 AN: 4810

European-Finnish (FIN) AF: 0.663 AC: 7025 AN: 10590

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.711 AC: 48072 AN: 67588

Other (OTH) AF: 0.727 AC: 1527 AN: 2100

Alfa AF: 0.743 Hom.: 5163

Bravo AF: 0.757

Asia WGS AF: 0.678 AC: 2357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.13
DANN	Benign	0.48
PhyloP100		-0.85
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: rs626316; hg19: chr6-65067582;