rs321498

Variant names:

• chr6-63869331-T-C
• rs321498
• NM_001142800.2:c.7056-4973A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-63869331-T-C
• chr6-63869331-T-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.7056-4973A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 151,908 control chromosomes in the GnomAD database, including 28,562 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 0.60 (28562 hom., cov: 31)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.7056-4973A>G		intron_variant	Intron 35 of 42	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.7056-4973A>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.7056-4973A>G		intron_variant	Intron 35 of 42	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.7056-4973A>G		intron_variant	Intron 35 of 43	1		ENSP00000359655.3
EYS	ENST00000398580.3	c.369-4973A>G		intron_variant	Intron 3 of 9	5		ENSP00000381585.3

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91514 AN: 151790 Hom.: 28558 Cov.: 31

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.706

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.673

Gnomad OTH AF: 0.612

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

GnomAD4 genome AF: 0.603 AC: 91546 AN: 151908 Hom.: 28562 Cov.: 31 AF XY: 0.604 AC XY: 44824 AN XY: 74232

African (AFR) AF: 0.451 AC: 18675 AN: 41428

American (AMR) AF: 0.577 AC: 8793 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 2014 AN: 3470

East Asian (EAS) AF: 0.707 AC: 3657 AN: 5172

South Asian (SAS) AF: 0.527 AC: 2536 AN: 4810

European-Finnish (FIN) AF: 0.765 AC: 8076 AN: 10550

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.673 AC: 45682 AN: 67926

Other (OTH) AF: 0.615 AC: 1298 AN: 2112

Alfa AF: 0.638 Hom.: 39577

Bravo AF: 0.584

Asia WGS AF: 0.629 AC: 2187 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.7
DANN	Benign	0.36
PhyloP100		-0.024
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: rs321498; hg19: chr6-64579224; COSMIC: COSV65482168;