NM_001142800.2:c.8071+84T>G

Variant names:

• chr6-63762377-A-C
• rs4710257
• NM_001142800.2:c.8071+84T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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 -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 VariationId 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 rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.8071+84T>G		intron_variant	Intron 41 of 42	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.8071+84T>G		intron_variant	Intron 41 of 43		NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.8071+84T>G		intron_variant	Intron 41 of 42	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.8071+84T>G		intron_variant	Intron 41 of 43	1		ENSP00000359655.3
EYS	ENST00000398580.3	c.1384+84T>G		intron_variant	Intron 9 of 9	5		ENSP00000381585.3
PHF3	ENST00000505138.1	c.362-15689A>C		intron_variant	Intron 3 of 4	3		ENSP00000421417.1

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

African (AFR) AF: 0.191 AC: 4656 AN: 24358

American (AMR) AF: 0.399 AC: 10360 AN: 25984

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 6490 AN: 21896

East Asian (EAS) AF: 0.244 AC: 8322 AN: 34168

South Asian (SAS) AF: 0.339 AC: 22742 AN: 67076

European-Finnish (FIN) AF: 0.232 AC: 11147 AN: 48096

Middle Eastern (MID) AF: 0.380 AC: 1324 AN: 3488

European-Non Finnish (NFE) AF: 0.339 AC: 288695 AN: 852162

Other (OTH) AF: 0.328 AC: 15819 AN: 48186

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

African (AFR) AF: 0.193 AC: 8021 AN: 41522

American (AMR) AF: 0.363 AC: 5540 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1046 AN: 3468

East Asian (EAS) AF: 0.283 AC: 1456 AN: 5142

South Asian (SAS) AF: 0.324 AC: 1565 AN: 4828

European-Finnish (FIN) AF: 0.219 AC: 2319 AN: 10574

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.327 AC: 22221 AN: 67916

Other (OTH) AF: 0.305 AC: 642 AN: 2108

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

May 11, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.9
DANN	Benign	0.81
PhyloP100		0.54
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: rs4710257; hg19: chr6-64472270; COSMIC: COSV65490589;