rs716618

Variant names:

• chr6-64003445-G-A
• rs716618
• NM_001142800.2:c.6726-4262C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-64003445-G-A
• chr6-64003445-G-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.6726-4262C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 151,984 control chromosomes in the GnomAD database, including 14,173 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 0.41 (14173 hom., cov: 32)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.913
• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142800.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	NM_001142800.2	MANE Select	c.6726-4262C>T		intron	N/A	NP_001136272.1	Q5T1H1-1
	EYS	NM_001292009.2		c.6726-4262C>T		intron	N/A	NP_001278938.1	Q5T1H1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	ENST00000503581.6	TSL:5 MANE Select	c.6726-4262C>T		intron	N/A	ENSP00000424243.1	Q5T1H1-1
	EYS	ENST00000370621.7	TSL:1	c.6726-4262C>T		intron	N/A	ENSP00000359655.3	Q5T1H1-3
	EYS	ENST00000398580.3	TSL:5	c.39-4262C>T		intron	N/A	ENSP00000381585.3	H0Y3Q4

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62712 AN: 151866 Hom.: 14140 Cov.: 32

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.421

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

GnomAD4 genome AF: 0.413 AC: 62792 AN: 151984 Hom.: 14173 Cov.: 32 AF XY: 0.406 AC XY: 30154 AN XY: 74292

African (AFR) AF: 0.608 AC: 25202 AN: 41458

American (AMR) AF: 0.304 AC: 4640 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1221 AN: 3470

East Asian (EAS) AF: 0.334 AC: 1725 AN: 5166

South Asian (SAS) AF: 0.354 AC: 1705 AN: 4812

European-Finnish (FIN) AF: 0.286 AC: 3015 AN: 10554

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.350 AC: 23755 AN: 67950

Other (OTH) AF: 0.416 AC: 876 AN: 2108

Alfa AF: 0.391 Hom.: 1632

Bravo AF: 0.425

Asia WGS AF: 0.329 AC: 1145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.65
DANN	Benign	0.081
PhyloP100		-0.91
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: rs716618; hg19: chr6-64713338;