rs644929

Variant names:

• chr6-64458883-A-G
• rs644929
• NM_001142800.2:c.5645-19531T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-64458883-A-G
• chr6-64458883-A-T

Variant summary

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

The NM_001142800.2(EYS):​c.5645-19531T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 151,946 control chromosomes in the GnomAD database, including 13,816 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 (13816 hom., cov: 32)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.940
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.5645-19531T>C		intron_variant	Intron 26 of 42	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.5645-19531T>C		intron_variant	Intron 26 of 43		NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.5645-19531T>C		intron_variant	Intron 26 of 42	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.5645-19531T>C		intron_variant	Intron 26 of 43	1		ENSP00000359655.3

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62264 AN: 151828 Hom.: 13778 Cov.: 32

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.410 AC: 62353 AN: 151946 Hom.: 13816 Cov.: 32 AF XY: 0.410 AC XY: 30441 AN XY: 74270

African (AFR) AF: 0.595 AC: 24657 AN: 41422

American (AMR) AF: 0.342 AC: 5225 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 977 AN: 3470

East Asian (EAS) AF: 0.500 AC: 2582 AN: 5162

South Asian (SAS) AF: 0.334 AC: 1613 AN: 4826

European-Finnish (FIN) AF: 0.360 AC: 3799 AN: 10540

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.325 AC: 22048 AN: 67922

Other (OTH) AF: 0.390 AC: 824 AN: 2112

Alfa AF: 0.195 Hom.: 474

Bravo AF: 0.422

Asia WGS AF: 0.403 AC: 1401 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.24
DANN	Benign	0.69
PhyloP100		-0.94
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: rs644929; hg19: chr6-65168776;