rs4509103

Variant names:

• chr6-64190337-G-T
• rs4509103
• NM_001142800.2:c.6424+40255C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001142800.2(EYS):​c.6424+40255C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0271 in 152,244 control chromosomes in the GnomAD database, including 59 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 0.027 (59 hom., cov: 32)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.178
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0271 (4124/152244) while in subpopulation AFR AF = 0.0425 (1764/41542). AF 95% confidence interval is 0.0408. There are 59 homozygotes in GnomAd4. There are 1984 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 59 AR,AD gene

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.6424+40255C>A		intron	N/A	NP_001136272.1	Q5T1H1-1
	EYS	NM_001292009.2		c.6424+40255C>A		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.6424+40255C>A		intron	N/A	ENSP00000424243.1	Q5T1H1-1
	EYS	ENST00000370621.7	TSL:1	c.6424+40255C>A		intron	N/A	ENSP00000359655.3	Q5T1H1-3

Frequencies

GnomAD3 genomes AF: 0.0271 AC: 4128 AN: 152126 Hom.: 59 Cov.: 32

Gnomad AFR AF: 0.0427

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0184

Gnomad ASJ AF: 0.00462

Gnomad EAS AF: 0.0349

Gnomad SAS AF: 0.0348

Gnomad FIN AF: 0.00999

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0228

Gnomad OTH AF: 0.0168

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

GnomAD4 genome AF: 0.0271 AC: 4124 AN: 152244 Hom.: 59 Cov.: 32 AF XY: 0.0266 AC XY: 1984 AN XY: 74450

African (AFR) AF: 0.0425 AC: 1764 AN: 41542

American (AMR) AF: 0.0184 AC: 281 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00462 AC: 16 AN: 3466

East Asian (EAS) AF: 0.0348 AC: 180 AN: 5178

South Asian (SAS) AF: 0.0350 AC: 169 AN: 4828

European-Finnish (FIN) AF: 0.00999 AC: 106 AN: 10614

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0228 AC: 1548 AN: 68008

Other (OTH) AF: 0.0166 AC: 35 AN: 2110

Alfa AF: 0.0263 Hom.: 8

Bravo AF: 0.0277

Asia WGS AF: 0.0250 AC: 87 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.51
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism

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: rs4509103; hg19: chr6-64900230;