chr6-64480020-G-A

Position:

• chr6-64480020-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001142800.2(EYS):​c.5645-40668C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0164 in 151,950 control chromosomes in the GnomAD database, including 23 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 0.016 (23 hom., cov: 32)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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=-0.92).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0164 (2496/151950) while in subpopulation SAS AF= 0.0352 (170/4826). AF 95% confidence interval is 0.0309. There are 23 homozygotes in gnomad4. There are 1251 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EYS	NM_001142800.2	c.5645-40668C>T		intron_variant		ENST00000503581.6
EYS	NM_001292009.2	c.5645-40668C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EYS	ENST00000503581.6	c.5645-40668C>T		intron_variant		5	NM_001142800.2	A2
EYS	ENST00000370621.7	c.5645-40668C>T		intron_variant		1		P2

Frequencies

GnomAD3 genomes AF: 0.0164 AC: 2496 AN: 151832 Hom.: 23 Cov.: 32

Gnomad AFR AF: 0.00401

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0136

Gnomad ASJ AF: 0.00434

Gnomad EAS AF: 0.0318

Gnomad SAS AF: 0.0350

Gnomad FIN AF: 0.0212

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0221

Gnomad OTH AF: 0.0125

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

GnomAD4 genome AF: 0.0164 AC: 2496 AN: 151950 Hom.: 23 Cov.: 32 AF XY: 0.0168 AC XY: 1251 AN XY: 74284

Gnomad4 AFR AF: 0.00400

Gnomad4 AMR AF: 0.0136

Gnomad4 ASJ AF: 0.00434

Gnomad4 EAS AF: 0.0317

Gnomad4 SAS AF: 0.0352

Gnomad4 FIN AF: 0.0212

Gnomad4 NFE AF: 0.0221

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.0174 Hom.: 2

Bravo AF: 0.0143

Asia WGS AF: 0.0220 AC: 77 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.44
DANN	Benign	0.88

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: rs7754782; hg19: chr6-65189913;