chr6-63862726-A-G

Variant names:

• chr6-63862726-A-G
• rs12205984
• NM_001142800.2:c.7228+1460T>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.7228+1460T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 152,122 control chromosomes in the GnomAD database, including 20,199 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 0.50 (20199 hom., cov: 32)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.279
• 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: 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).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.7228+1460T>C		intron_variant	Intron 36 of 42	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.7228+1460T>C		intron_variant	Intron 36 of 43		NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.7228+1460T>C		intron_variant	Intron 36 of 42	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.7228+1460T>C		intron_variant	Intron 36 of 43	1		ENSP00000359655.3
EYS	ENST00000398580.3	c.541+1460T>C		intron_variant	Intron 4 of 9	5		ENSP00000381585.3

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75514 AN: 152004 Hom.: 20152 Cov.: 32

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.455

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

GnomAD4 genome AF: 0.497 AC: 75617 AN: 152122 Hom.: 20199 Cov.: 32 AF XY: 0.497 AC XY: 36982 AN XY: 74376

African (AFR) AF: 0.687 AC: 28510 AN: 41496

American (AMR) AF: 0.527 AC: 8062 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1654 AN: 3468

East Asian (EAS) AF: 0.459 AC: 2379 AN: 5182

South Asian (SAS) AF: 0.540 AC: 2604 AN: 4822

European-Finnish (FIN) AF: 0.331 AC: 3500 AN: 10578

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.404 AC: 27478 AN: 67974

Other (OTH) AF: 0.451 AC: 952 AN: 2112

Alfa AF: 0.447 Hom.: 29031

Bravo AF: 0.520

Asia WGS AF: 0.464 AC: 1612 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.1
DANN	Benign	0.73
PhyloP100		0.28
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: rs12205984; hg19: chr6-64572619;