chr6-64357511-C-A

Variant names:

• chr6-64357511-C-A
• rs10944484
• NM_001142800.2:c.6078+31179G>T

Variant summary

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

The NM_001142800.2(EYS):​c.6078+31179G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 151,560 control chromosomes in the GnomAD database, including 2,358 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 0.16 (2358 hom., cov: 34)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.323
• Publications: 2 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.291 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.6078+31179G>T		intron	N/A	NP_001136272.1	Q5T1H1-1
	EYS	NM_001292009.2		c.6078+31179G>T		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.6078+31179G>T		intron	N/A	ENSP00000424243.1	Q5T1H1-1
	EYS	ENST00000370621.7	TSL:1	c.6078+31179G>T		intron	N/A	ENSP00000359655.3	Q5T1H1-3

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23826 AN: 151442 Hom.: 2356 Cov.: 34

Gnomad AFR AF: 0.0394

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.0883

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.157 AC: 23825 AN: 151560 Hom.: 2358 Cov.: 34 AF XY: 0.157 AC XY: 11639 AN XY: 74064

African (AFR) AF: 0.0393 AC: 1630 AN: 41452

American (AMR) AF: 0.280 AC: 4260 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 535 AN: 3456

East Asian (EAS) AF: 0.304 AC: 1548 AN: 5096

South Asian (SAS) AF: 0.0881 AC: 425 AN: 4822

European-Finnish (FIN) AF: 0.179 AC: 1894 AN: 10574

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 12942 AN: 67652

Other (OTH) AF: 0.176 AC: 369 AN: 2102

Alfa AF: 0.179 Hom.: 5337

Bravo AF: 0.163

Asia WGS AF: 0.167 AC: 579 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.7
DANN	Benign	0.55
PhyloP100		-0.32
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: rs10944484; hg19: chr6-65067404;