chr6-63777354-A-G

Variant names:

• chr6-63777354-A-G
• rs319924
• NM_001142800.2:c.7898+652T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001292009.2(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_001292009.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.276
• 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]

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001292009.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	NM_001142800.2	MANE Select	c.7898+652T>C		intron	N/A	NP_001136272.1
	EYS	NM_001292009.2		c.7898+652T>C		intron	N/A	NP_001278938.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	ENST00000503581.6	TSL:5 MANE Select	c.7898+652T>C		intron	N/A	ENSP00000424243.1
	EYS	ENST00000370621.7	TSL:1	c.7898+652T>C		intron	N/A	ENSP00000359655.3
	EYS	ENST00000398580.3	TSL:5	c.1211+652T>C		intron	N/A	ENSP00000381585.3

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

African (AFR) AF: 0.749 AC: 31023 AN: 41434

American (AMR) AF: 0.536 AC: 8172 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.461 AC: 1600 AN: 3470

East Asian (EAS) AF: 0.460 AC: 2363 AN: 5136

South Asian (SAS) AF: 0.534 AC: 2572 AN: 4816

European-Finnish (FIN) AF: 0.331 AC: 3487 AN: 10548

Middle Eastern (MID) AF: 0.459 AC: 134 AN: 292

European-Non Finnish (NFE) AF: 0.401 AC: 27236 AN: 67942

Other (OTH) AF: 0.470 AC: 992 AN: 2110

Alfa AF: 0.448 Hom.: 48998

Bravo AF: 0.539

Asia WGS AF: 0.469 AC: 1630 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	5.1
DANN	Benign	0.68
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs319924; hg19: chr6-64487247;