rs34154043

Variant names:

• chr6-65405388-GA-G
• rs34154043
• NM_001142800.2:c.863-22delT

Your query was ambiguous. Multiple possible variants found:

• chr6-65405388-GA-G
• chr6-65405388-GA-GAA
• chr6-65405388-GA-GAAA
• chr6-65405388-GA-GAAAA
• chr6-65405388-GA-GAAAAA
• chr6-65405388-GA-GAAAAAA
• chr6-65405388-GA-GAAAAAAA
• chr6-65405388-GA-GAAAAAAAAAAAAAAAAAA

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001142800.2(EYS):​c.863-22delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00297 in 1,485,430 control chromosomes in the GnomAD database, including 27 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0023 (3 hom., cov: 0)
  • Exomes 𝑓: 0.0030 (24 hom.)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.391
• Publications: 4 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 3 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.863-22delT		intron_variant	Intron 5 of 42	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.863-22delT		intron_variant	Intron 5 of 43		NP_001278938.1
EYS	NM_001142801.2	c.863-22delT		intron_variant	Intron 5 of 11		NP_001136273.1
EYS	NM_198283.2	c.863-22delT		intron_variant	Intron 4 of 9		NP_938024.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.863-22delT		intron_variant	Intron 5 of 42	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.863-22delT		intron_variant	Intron 5 of 43	1		ENSP00000359655.3
EYS	ENST00000393380.6	c.863-22delT		intron_variant	Intron 5 of 11	1		ENSP00000377042.2
EYS	ENST00000342421.9	c.863-22delT		intron_variant	Intron 3 of 8	1		ENSP00000341818.5

Frequencies

GnomAD3 genomes AF: 0.00233 AC: 345 AN: 148276 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.000570

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00552

Gnomad ASJ AF: 0.000290

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000211

Gnomad FIN AF: 0.000420

Gnomad MID AF: 0.00641

Gnomad NFE AF: 0.00337

Gnomad OTH AF: 0.00294

GnomAD2 exomes AF: 0.00246 AC: 499 AN: 202572 AF XY: 0.00256

Gnomad AFR exome AF: 0.000808

Gnomad AMR exome AF: 0.00401

Gnomad ASJ exome AF: 0.00125

Gnomad EAS exome AF: 0.0000692

Gnomad FIN exome AF: 0.000325

Gnomad NFE exome AF: 0.00340

Gnomad OTH exome AF: 0.00403

GnomAD4 exome AF: 0.00304 AC: 4064 AN: 1337052 Hom.: 24 Cov.: 25 AF XY: 0.00305 AC XY: 2039 AN XY: 669014

African (AFR) AF: 0.000499 AC: 15 AN: 30070

American (AMR) AF: 0.00363 AC: 139 AN: 38294

Ashkenazi Jewish (ASJ) AF: 0.00103 AC: 25 AN: 24172

East Asian (EAS) AF: 0.0000791 AC: 3 AN: 37924

South Asian (SAS) AF: 0.00109 AC: 84 AN: 76992

European-Finnish (FIN) AF: 0.000505 AC: 26 AN: 51438

Middle Eastern (MID) AF: 0.00281 AC: 15 AN: 5340

European-Non Finnish (NFE) AF: 0.00352 AC: 3578 AN: 1017254

Other (OTH) AF: 0.00322 AC: 179 AN: 55568

GnomAD4 genome AF: 0.00233 AC: 345 AN: 148378 Hom.: 3 Cov.: 0 AF XY: 0.00251 AC XY: 181 AN XY: 72244

African (AFR) AF: 0.000568 AC: 23 AN: 40502

American (AMR) AF: 0.00551 AC: 82 AN: 14886

Ashkenazi Jewish (ASJ) AF: 0.000290 AC: 1 AN: 3448

East Asian (EAS) AF: 0.00 AC: 0 AN: 5040

South Asian (SAS) AF: 0.000212 AC: 1 AN: 4726

European-Finnish (FIN) AF: 0.000420 AC: 4 AN: 9528

Middle Eastern (MID) AF: 0.00690 AC: 2 AN: 290

European-Non Finnish (NFE) AF: 0.00337 AC: 226 AN: 66996

Other (OTH) AF: 0.00291 AC: 6 AN: 2060

Alfa AF: 0.00204 Hom.: 270

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.39
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: rs34154043; hg19: chr6-66115281;