6-63777354-A-G

Position:

• chr6-63777354-A-G

Variant summary

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

The NM_001142800.2(EYS):​c.7898+652T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 151,904 control chromosomes in the GnomAD database, including 21,975 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 0.51 (21975 hom., cov: 31)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.276

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]

PHF3 (HGNC:8921): (PHD finger protein 3) This gene encodes a member of a PHD finger-containing gene family. This gene may function as a transcription factor and may be involved in glioblastomas development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EYS	NM_001142800.2	c.7898+652T>C		intron_variant		ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.7898+652T>C		intron_variant			NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.7898+652T>C		intron_variant		5	NM_001142800.2	ENSP00000424243	A2
EYS	ENST00000370621.7	c.7898+652T>C		intron_variant		1		ENSP00000359655	P2
EYS	ENST00000398580.3	c.1212+652T>C		intron_variant		5		ENSP00000381585
PHF3	ENST00000505138.1	c.364-712A>G		intron_variant		3		ENSP00000421417

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77855 AN: 151786 Hom.: 21925 Cov.: 31

Gnomad AFR AF: 0.749

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.474

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

GnomAD4 genome AF: 0.513 AC: 77963 AN: 151904 Hom.: 21975 Cov.: 31 AF XY: 0.513 AC XY: 38047 AN XY: 74228

Gnomad4 AFR AF: 0.749

Gnomad4 AMR AF: 0.536

Gnomad4 ASJ AF: 0.461

Gnomad4 EAS AF: 0.460

Gnomad4 SAS AF: 0.534

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.401

Gnomad4 OTH AF: 0.470

Alfa AF: 0.425 Hom.: 27429

Bravo AF: 0.539

Asia WGS AF: 0.469 AC: 1630 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	5.1
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs319924; hg19: chr6-64487247;