chr6-64461526-T-C

Variant names:

• chr6-64461526-T-C
• rs9351261
• NM_001142800.2:c.5645-22174A>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.5645-22174A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 152,022 control chromosomes in the GnomAD database, including 8,843 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 0.34 (8843 hom., cov: 32)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.130
• 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: 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.424 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.5645-22174A>G		intron	N/A	NP_001136272.1	Q5T1H1-1
	EYS	NM_001292009.2		c.5645-22174A>G		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.5645-22174A>G		intron	N/A	ENSP00000424243.1	Q5T1H1-1
	EYS	ENST00000370621.7	TSL:1	c.5645-22174A>G		intron	N/A	ENSP00000359655.3	Q5T1H1-3

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51356 AN: 151904 Hom.: 8845 Cov.: 32

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.338 AC: 51370 AN: 152022 Hom.: 8843 Cov.: 32 AF XY: 0.340 AC XY: 25264 AN XY: 74296

African (AFR) AF: 0.254 AC: 10525 AN: 41444

American (AMR) AF: 0.324 AC: 4947 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1335 AN: 3466

East Asian (EAS) AF: 0.439 AC: 2266 AN: 5162

South Asian (SAS) AF: 0.365 AC: 1761 AN: 4824

European-Finnish (FIN) AF: 0.406 AC: 4281 AN: 10556

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.367 AC: 24963 AN: 67972

Other (OTH) AF: 0.352 AC: 744 AN: 2114

Alfa AF: 0.363 Hom.: 20757

Bravo AF: 0.330

Asia WGS AF: 0.382 AC: 1331 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.81
DANN	Benign	0.64
PhyloP100		-0.13
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: rs9351261; hg19: chr6-65171419;