rs3857532

Variant names:

• chr6-64523772-G-A
• rs3857532
• NM_001142800.2:c.5644+66451C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-64523772-G-A
• chr6-64523772-G-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.5644+66451C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 151,428 control chromosomes in the GnomAD database, including 13,592 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 0.42 (13592 hom., cov: 32)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.372
• Publications: 6 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.5644+66451C>T		intron_variant	Intron 26 of 42	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.5644+66451C>T		intron_variant	Intron 26 of 43		NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.5644+66451C>T		intron_variant	Intron 26 of 42	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.5644+66451C>T		intron_variant	Intron 26 of 43	1		ENSP00000359655.3

Frequencies

GnomAD3 genomes AF: 0.415 AC: 62776 AN: 151308 Hom.: 13567 Cov.: 32

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.415 AC: 62857 AN: 151428 Hom.: 13592 Cov.: 32 AF XY: 0.415 AC XY: 30687 AN XY: 73982

African (AFR) AF: 0.560 AC: 23167 AN: 41350

American (AMR) AF: 0.352 AC: 5343 AN: 15176

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1177 AN: 3456

East Asian (EAS) AF: 0.500 AC: 2574 AN: 5146

South Asian (SAS) AF: 0.329 AC: 1590 AN: 4830

European-Finnish (FIN) AF: 0.387 AC: 4075 AN: 10534

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.348 AC: 23527 AN: 67632

Other (OTH) AF: 0.399 AC: 839 AN: 2102

Alfa AF: 0.378 Hom.: 1985

Bravo AF: 0.424

Asia WGS AF: 0.397 AC: 1379 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.4
DANN	Benign	0.25
PhyloP100		0.37
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: rs3857532; hg19: chr6-65233665;