rs4710257

chr6-63762377-A-Cchr6-63762377-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001142800.2(EYS):c.8071+84T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 1,277,418 control chromosomes in the GnomAD database, including 68,460 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (6424 hom., cov: 32)
  • Exomes 𝑓: 0.33 (62036 hom.)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.544

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 6-63762377-A-C is Benign according to our data. Variant chr6-63762377-A-C is described in ClinVar as [Benign]. Clinvar id is 1246986.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EYS	NM_001142800.2	c.8071+84T>G		intron_variant		ENST00000503581.6
EYS	NM_001292009.2	c.8071+84T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EYS	ENST00000503581.6	c.8071+84T>G		intron_variant		5	NM_001142800.2	A2
EYS	ENST00000370621.7	c.8071+84T>G		intron_variant		1		P2
EYS	ENST00000398580.3	c.1385+84T>G		intron_variant		5
PHF3	ENST00000505138.1	c.364-15689A>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43220 AN: 151886 Hom.: 6419 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.308

GnomAD4 exome AF: 0.328 AC: 369555 AN: 1125414 Hom.: 62036 AF XY: 0.329 AC XY: 185481 AN XY: 563962

Gnomad4 AFR exome AF: 0.191

Gnomad4 AMR exome AF: 0.399

Gnomad4 ASJ exome AF: 0.296

Gnomad4 EAS exome AF: 0.244

Gnomad4 SAS exome AF: 0.339

Gnomad4 FIN exome AF: 0.232

Gnomad4 NFE exome AF: 0.339

Gnomad4 OTH exome AF: 0.328

GnomAD4 genome AF: 0.284 AC: 43233 AN: 152004 Hom.: 6424 Cov.: 32 AF XY: 0.283 AC XY: 21012 AN XY: 74302

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.363

Gnomad4 ASJ AF: 0.302

Gnomad4 EAS AF: 0.283

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.305

Alfa AF: 0.292 Hom.: 837

Bravo AF: 0.293

Asia WGS AF: 0.279 AC: 968 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	6.9
Dann	Benign	0.81

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: rs4710257; hg19: chr6-64472270; COSMIC: COSV65490589;