rs13197839

Variant names:

• chr6-65279399-A-C
• rs13197839
• NM_001142800.2:c.2023+16464T>G

Your query was ambiguous. Multiple possible variants found:

• chr6-65279399-A-C
• chr6-65279399-A-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.2023+16464T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 151,990 control chromosomes in the GnomAD database, including 3,512 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 0.20 (3512 hom., cov: 31)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.368
• Publications: 3 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.2023+16464T>G		intron_variant	Intron 12 of 42	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.2023+16464T>G		intron_variant	Intron 12 of 43		NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.2023+16464T>G		intron_variant	Intron 12 of 42	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.2023+16464T>G		intron_variant	Intron 12 of 43	1		ENSP00000359655.3

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29800 AN: 151872 Hom.: 3515 Cov.: 31

Gnomad AFR AF: 0.0863

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.0583

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.178

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

GnomAD4 genome AF: 0.196 AC: 29797 AN: 151990 Hom.: 3512 Cov.: 31 AF XY: 0.195 AC XY: 14522 AN XY: 74292

African (AFR) AF: 0.0861 AC: 3573 AN: 41498

American (AMR) AF: 0.171 AC: 2613 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1192 AN: 3468

East Asian (EAS) AF: 0.0580 AC: 299 AN: 5154

South Asian (SAS) AF: 0.128 AC: 616 AN: 4824

European-Finnish (FIN) AF: 0.327 AC: 3449 AN: 10562

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.258 AC: 17501 AN: 67922

Other (OTH) AF: 0.176 AC: 372 AN: 2112

Alfa AF: 0.215 Hom.: 3344

Bravo AF: 0.179

Asia WGS AF: 0.0970 AC: 339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.62
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: rs13197839; hg19: chr6-65989292;