NM_001142800.2:c.6079-34554T>C

Variant names:

• chr6-64341636-A-G
• rs12208631
• NM_001142800.2:c.6079-34554T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001142800.2(EYS):​c.6079-34554T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0277 in 151,790 control chromosomes in the GnomAD database, including 88 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 0.028 (88 hom., cov: 32)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240
• 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=-0.91).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0277 (4200/151790) while in subpopulation NFE AF = 0.0407 (2757/67748). AF 95% confidence interval is 0.0394. There are 88 homozygotes in GnomAd4. There are 1994 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 88 AR,AD gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	NM_001142800.2	MANE Select	c.6079-34554T>C		intron	N/A	NP_001136272.1
	EYS	NM_001292009.2		c.6079-34554T>C		intron	N/A	NP_001278938.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	ENST00000503581.6	TSL:5 MANE Select	c.6079-34554T>C		intron	N/A	ENSP00000424243.1
	EYS	ENST00000370621.7	TSL:1	c.6079-34554T>C		intron	N/A	ENSP00000359655.3

Frequencies

GnomAD3 genomes AF: 0.0277 AC: 4199 AN: 151672 Hom.: 87 Cov.: 32

Gnomad AFR AF: 0.00705

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0232

Gnomad ASJ AF: 0.0916

Gnomad EAS AF: 0.000195

Gnomad SAS AF: 0.0226

Gnomad FIN AF: 0.0260

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0407

Gnomad OTH AF: 0.0400

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

GnomAD4 genome AF: 0.0277 AC: 4200 AN: 151790 Hom.: 88 Cov.: 32 AF XY: 0.0269 AC XY: 1994 AN XY: 74174

African (AFR) AF: 0.00703 AC: 292 AN: 41518

American (AMR) AF: 0.0232 AC: 352 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.0916 AC: 317 AN: 3462

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5128

South Asian (SAS) AF: 0.0228 AC: 110 AN: 4824

European-Finnish (FIN) AF: 0.0260 AC: 276 AN: 10614

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0407 AC: 2757 AN: 67748

Other (OTH) AF: 0.0396 AC: 83 AN: 2098

Alfa AF: 0.0287 Hom.: 42

Bravo AF: 0.0264

Asia WGS AF: 0.0110 AC: 37 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.3
DANN	Benign	0.63
PhyloP100		0.24
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: rs12208631; hg19: chr6-65051529;