6-64926030-C-G

Variant names:

• chr6-64926030-C-G
• rs11754641
• NM_001142800.2:c.2382-13287G>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.2382-13287G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.032 in 152,212 control chromosomes in the GnomAD database, including 133 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 0.032 (133 hom., cov: 32)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.691
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.2382-13287G>C		intron_variant	Intron 15 of 42	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.2382-13287G>C		intron_variant	Intron 15 of 43		NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.2382-13287G>C		intron_variant	Intron 15 of 42	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.2382-13287G>C		intron_variant	Intron 15 of 43	1		ENSP00000359655.3

Frequencies

GnomAD3 genomes AF: 0.0321 AC: 4878 AN: 152094 Hom.: 134 Cov.: 32

Gnomad AFR AF: 0.00883

Gnomad AMI AF: 0.0989

Gnomad AMR AF: 0.0532

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.0205

Gnomad FIN AF: 0.00998

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0385

Gnomad OTH AF: 0.0330

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

GnomAD4 genome AF: 0.0320 AC: 4874 AN: 152212 Hom.: 133 Cov.: 32 AF XY: 0.0317 AC XY: 2357 AN XY: 74422

African (AFR) AF: 0.00881 AC: 366 AN: 41554

American (AMR) AF: 0.0533 AC: 816 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0127 AC: 44 AN: 3470

East Asian (EAS) AF: 0.129 AC: 662 AN: 5142

South Asian (SAS) AF: 0.0203 AC: 98 AN: 4820

European-Finnish (FIN) AF: 0.00998 AC: 106 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0385 AC: 2616 AN: 67996

Other (OTH) AF: 0.0327 AC: 69 AN: 2112

Alfa AF: 0.0144 Hom.: 7

Bravo AF: 0.0353

Asia WGS AF: 0.0590 AC: 204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.40
DANN	Benign	0.46
PhyloP100		-0.69
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: rs11754641; hg19: chr6-65635923;