chr6-63729023-G-T

Variant names:

• chr6-63729023-G-T
• rs12205302
• NM_001142800.2:c.8072-2343C>A

Variant summary

Our verdict is Benign. The variant received -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
• 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 = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.8072-2343C>A		intron_variant	Intron 41 of 42	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.8135-2343C>A		intron_variant	Intron 42 of 43		NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.8072-2343C>A		intron_variant	Intron 41 of 42	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.8135-2343C>A		intron_variant	Intron 42 of 43	1		ENSP00000359655.3
PHF3	ENST00000505138.1	c.361+17661G>T		intron_variant	Intron 3 of 4	3		ENSP00000421417.1

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

African (AFR) AF: 0.737 AC: 30574 AN: 41458

American (AMR) AF: 0.553 AC: 8434 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1632 AN: 3466

East Asian (EAS) AF: 0.456 AC: 2352 AN: 5156

South Asian (SAS) AF: 0.562 AC: 2710 AN: 4824

European-Finnish (FIN) AF: 0.358 AC: 3757 AN: 10494

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.450 AC: 30537 AN: 67924

Other (OTH) AF: 0.499 AC: 1055 AN: 2114

Alfa AF: 0.455 Hom.: 15821

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
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12205302; hg19: chr6-64438916;