6-63729023-G-T

Variant summary

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

The NM_001142800.2(EYS):c.8072-2343C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 151,886 control chromosomes in the GnomAD database, including 23,354 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 0.54 (23354 hom., cov: 31)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.114

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 = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EYS	NM_001142800.2	c.8072-2343C>A		intron_variant		ENST00000503581.6
EYS	NM_001292009.2	c.8135-2343C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EYS	ENST00000503581.6	c.8072-2343C>A		intron_variant		5	NM_001142800.2	A2
EYS	ENST00000370621.7	c.8135-2343C>A		intron_variant		1		P2
PHF3	ENST00000505138.1	c.363+17661G>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81528 AN: 151768 Hom.: 23303 Cov.: 31

Gnomad AFR AF: 0.737

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.503

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

GnomAD4 genome AF: 0.537 AC: 81636 AN: 151886 Hom.: 23354 Cov.: 31 AF XY: 0.536 AC XY: 39774 AN XY: 74196

Gnomad4 AFR AF: 0.737

Gnomad4 AMR AF: 0.553

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.456

Gnomad4 SAS AF: 0.562

Gnomad4 FIN AF: 0.358

Gnomad4 NFE AF: 0.450

Gnomad4 OTH AF: 0.499

Alfa AF: 0.453 Hom.: 14769

Bravo AF: 0.561

Asia WGS AF: 0.483 AC: 1677 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.48
Dann	Benign	0.51

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: rs12205302; hg19: chr6-64438916;