6-64274758-C-T

Variant names:

• chr6-64274758-C-T
• rs9353681
• NM_001142800.2:c.6191+32212G>A

Variant summary

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

The NM_001142800.2(EYS):​c.6191+32212G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 151,912 control chromosomes in the GnomAD database, including 3,977 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 0.21 (3977 hom., cov: 30)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.264
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.6191+32212G>A		intron_variant	Intron 30 of 42	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.6191+32212G>A		intron_variant	Intron 30 of 43		NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.6191+32212G>A		intron_variant	Intron 30 of 42	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.6191+32212G>A		intron_variant	Intron 30 of 43	1		ENSP00000359655.3

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31562 AN: 151794 Hom.: 3975 Cov.: 30

Gnomad AFR AF: 0.0504

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.241

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

GnomAD4 genome AF: 0.208 AC: 31560 AN: 151912 Hom.: 3977 Cov.: 30 AF XY: 0.209 AC XY: 15524 AN XY: 74214

African (AFR) AF: 0.0503 AC: 2086 AN: 41466

American (AMR) AF: 0.324 AC: 4935 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 690 AN: 3472

East Asian (EAS) AF: 0.305 AC: 1572 AN: 5160

South Asian (SAS) AF: 0.195 AC: 940 AN: 4810

European-Finnish (FIN) AF: 0.252 AC: 2651 AN: 10508

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.263 AC: 17886 AN: 67938

Other (OTH) AF: 0.239 AC: 503 AN: 2108

Alfa AF: 0.246 Hom.: 9455

Bravo AF: 0.209

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.4
DANN	Benign	0.80
PhyloP100		-0.26
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: rs9353681; hg19: chr6-64984651;