rs3003672

Variant names:

• chr6-64121227-A-C
• rs3003672
• NM_001142800.2:c.6425-39225T>G

Your query was ambiguous. Multiple possible variants found:

• chr6-64121227-A-C
• chr6-64121227-A-G

Variant summary

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

The NM_001142800.2(EYS):​c.6425-39225T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0831 in 152,224 control chromosomes in the GnomAD database, including 1,375 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 0.083 (1375 hom., cov: 32)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.205
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.251 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	NM_001142800.2	MANE Select	c.6425-39225T>G		intron	N/A	NP_001136272.1
	EYS	NM_001292009.2		c.6425-39225T>G		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.6425-39225T>G		intron	N/A	ENSP00000424243.1
	EYS	ENST00000370621.7	TSL:1	c.6425-39225T>G		intron	N/A	ENSP00000359655.3

Frequencies

GnomAD3 genomes AF: 0.0830 AC: 12630 AN: 152106 Hom.: 1374 Cov.: 32

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0481

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.0791

Gnomad SAS AF: 0.0153

Gnomad FIN AF: 0.0463

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00322

Gnomad OTH AF: 0.0612

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

GnomAD4 genome AF: 0.0831 AC: 12653 AN: 152224 Hom.: 1375 Cov.: 32 AF XY: 0.0824 AC XY: 6136 AN XY: 74432

African (AFR) AF: 0.255 AC: 10585 AN: 41482

American (AMR) AF: 0.0483 AC: 740 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3468

East Asian (EAS) AF: 0.0787 AC: 408 AN: 5186

South Asian (SAS) AF: 0.0151 AC: 73 AN: 4830

European-Finnish (FIN) AF: 0.0463 AC: 491 AN: 10606

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00322 AC: 219 AN: 68026

Other (OTH) AF: 0.0616 AC: 130 AN: 2112

Alfa AF: 0.0228 Hom.: 448

Bravo AF: 0.0924

Asia WGS AF: 0.0590 AC: 203 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.91
DANN	Benign	0.32
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: rs3003672; hg19: chr6-64831120;