6-65353453-G-T

Position:

• chr6-65353453-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001142800.2(EYS):​c.1459+5C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: EYS NM_001142800.2 splice_region, intron
• Scores: Splicing: ADA: 0.00005954
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.270

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EYS	NM_001142800.2	c.1459+5C>A		splice_region_variant, intron_variant		ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.1459+5C>A		splice_region_variant, intron_variant			NP_001278938.1
EYS	NM_001142801.2	c.1459+5C>A		splice_region_variant, intron_variant			NP_001136273.1
EYS	NM_198283.2	c.1459+5C>A		splice_region_variant, intron_variant			NP_938024.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.1459+5C>A		splice_region_variant, intron_variant		5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.1459+5C>A		splice_region_variant, intron_variant		1		ENSP00000359655.3
EYS	ENST00000393380.6	c.1459+5C>A		splice_region_variant, intron_variant		1		ENSP00000377042.2
EYS	ENST00000342421.9	c.1459+5C>A		splice_region_variant, intron_variant		1		ENSP00000341818.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460190 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726428

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.6
DANN	Benign	0.32

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000060
dbscSNV1_RF	Benign	0.0040
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: rs200387978; hg19: chr6-66063346;