rs10944813

chr6-65497325-A-Gchr6-65497325-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142800.2(EYS):c.-332-1332T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 151,838 control chromosomes in the GnomAD database, including 7,047 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 0.30 (7047 hom., cov: 32)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0920

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EYS	NM_001142800.2	c.-332-1332T>C		intron_variant		ENST00000503581.6
EYS	NM_001142801.2	c.-332-1332T>C		intron_variant
EYS	NM_001292009.2	c.-332-1332T>C		intron_variant
EYS	NM_198283.2	c.-332-1332T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EYS	ENST00000503581.6	c.-332-1332T>C		intron_variant		5	NM_001142800.2	A2
EYS	ENST00000370621.7	c.-332-1332T>C		intron_variant		1		P2
EYS	ENST00000393380.6	c.-332-1332T>C		intron_variant		1
EYS	ENST00000489873.1	n.196-1332T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45086 AN: 151720 Hom.: 7026 Cov.: 32

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.297 AC: 45162 AN: 151838 Hom.: 7047 Cov.: 32 AF XY: 0.297 AC XY: 22026 AN XY: 74240

Gnomad4 AFR AF: 0.387

Gnomad4 AMR AF: 0.338

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.246

Gnomad4 OTH AF: 0.328

Alfa AF: 0.266 Hom.: 5142

Bravo AF: 0.312

Asia WGS AF: 0.256 AC: 891 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	1.5
Dann	Benign	0.34

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

Publications

LitVar

Other links and lift over

dbSNP: rs10944813; hg19: chr6-66207218;