chr6-63885181-T-C

Variant names:

• chr6-63885181-T-C
• rs729291
• NM_001142800.2:c.7056-20823A>G

Variant summary

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

The NM_001142800.2(EYS):​c.7056-20823A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 151,956 control chromosomes in the GnomAD database, including 20,624 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 (20624 hom., cov: 32)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.599
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.7056-20823A>G		intron_variant	Intron 35 of 42	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.7056-20823A>G		intron_variant	Intron 35 of 43		NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.7056-20823A>G		intron_variant	Intron 35 of 42	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.7056-20823A>G		intron_variant	Intron 35 of 43	1		ENSP00000359655.3
EYS	ENST00000398580.3	c.369-20823A>G		intron_variant	Intron 3 of 9	5		ENSP00000381585.3

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76179 AN: 151838 Hom.: 20579 Cov.: 32

Gnomad AFR AF: 0.696

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.462

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

GnomAD4 genome AF: 0.502 AC: 76281 AN: 151956 Hom.: 20624 Cov.: 32 AF XY: 0.502 AC XY: 37277 AN XY: 74286

African (AFR) AF: 0.696 AC: 28878 AN: 41466

American (AMR) AF: 0.536 AC: 8185 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1649 AN: 3464

East Asian (EAS) AF: 0.460 AC: 2377 AN: 5168

South Asian (SAS) AF: 0.539 AC: 2595 AN: 4812

European-Finnish (FIN) AF: 0.332 AC: 3507 AN: 10548

Middle Eastern (MID) AF: 0.459 AC: 134 AN: 292

European-Non Finnish (NFE) AF: 0.407 AC: 27651 AN: 67936

Other (OTH) AF: 0.458 AC: 962 AN: 2102

Alfa AF: 0.443 Hom.: 9558

Bravo AF: 0.525

Asia WGS AF: 0.469 AC: 1631 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.29
DANN	Benign	0.40
PhyloP100		-0.60
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: rs729291; hg19: chr6-64595074;