rs756274

Variant names:

• chr6-63795320-A-G
• rs756274
• NM_001142800.2:c.7412-6096T>C

Variant summary

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

The NM_001142800.2(EYS):​c.7412-6096T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 152,074 control chromosomes in the GnomAD database, including 12,267 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 0.39 (12267 hom., cov: 32)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.496
• Publications: 6 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.7412-6096T>C		intron_variant	Intron 37 of 42	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.7412-6096T>C		intron_variant	Intron 37 of 43		NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.7412-6096T>C		intron_variant	Intron 37 of 42	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.7412-6096T>C		intron_variant	Intron 37 of 43	1		ENSP00000359655.3
EYS	ENST00000398580.3	c.725-6096T>C		intron_variant	Intron 5 of 9	5		ENSP00000381585.3
EYS	ENST00000486069.1	n.52-6096T>C		intron_variant	Intron 1 of 5	3

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59588 AN: 151956 Hom.: 12251 Cov.: 32

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.392 AC: 59628 AN: 152074 Hom.: 12267 Cov.: 32 AF XY: 0.387 AC XY: 28787 AN XY: 74332

African (AFR) AF: 0.510 AC: 21138 AN: 41480

American (AMR) AF: 0.422 AC: 6441 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1202 AN: 3464

East Asian (EAS) AF: 0.284 AC: 1470 AN: 5172

South Asian (SAS) AF: 0.361 AC: 1744 AN: 4826

European-Finnish (FIN) AF: 0.222 AC: 2348 AN: 10594

Middle Eastern (MID) AF: 0.387 AC: 113 AN: 292

European-Non Finnish (NFE) AF: 0.354 AC: 24026 AN: 67958

Other (OTH) AF: 0.385 AC: 813 AN: 2112

Alfa AF: 0.380 Hom.: 24242

Bravo AF: 0.413

Asia WGS AF: 0.307 AC: 1066 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.4
DANN	Benign	0.66
PhyloP100		-0.50
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: rs756274; hg19: chr6-64505213;