chr6-64388622-T-C

Variant names:

• chr6-64388622-T-C
• rs36133910
• NM_001142800.2:c.6078+68A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001142800.2(EYS):​c.6078+68A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 1,345,756 control chromosomes in the GnomAD database, including 60,109 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (5960 hom., cov: 32)
  • Exomes 𝑓: 0.30 (54149 hom.)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.562
• 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]

EYS Gene-Disease associations (from GenCC):

• EYS-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• retinitis pigmentosa

  Inheritance: AR, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
• retinitis pigmentosa 25

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ENSG00000232120 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 6-64388622-T-C is Benign according to our data. Variant chr6-64388622-T-C is described in ClinVar as Benign. ClinVar VariationId is 1175357.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.6078+68A>G		intron_variant	Intron 29 of 42	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.6078+68A>G		intron_variant	Intron 29 of 43		NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.6078+68A>G		intron_variant	Intron 29 of 42	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.6078+68A>G		intron_variant	Intron 29 of 43	1		ENSP00000359655.3
ENSG00000232120	ENST00000424274.1	n.267+8910T>C		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42119 AN: 151888 Hom.: 5956 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.296

GnomAD4 exome AF: 0.298 AC: 356260 AN: 1193748 Hom.: 54149 AF XY: 0.298 AC XY: 175928 AN XY: 589550

African (AFR) AF: 0.205 AC: 4959 AN: 24148

American (AMR) AF: 0.296 AC: 4539 AN: 15342

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 6085 AN: 21088

East Asian (EAS) AF: 0.459 AC: 14327 AN: 31230

South Asian (SAS) AF: 0.291 AC: 16389 AN: 56248

European-Finnish (FIN) AF: 0.350 AC: 13950 AN: 39844

Middle Eastern (MID) AF: 0.296 AC: 1174 AN: 3972

European-Non Finnish (NFE) AF: 0.294 AC: 279701 AN: 952068

Other (OTH) AF: 0.304 AC: 15136 AN: 49808

GnomAD4 genome AF: 0.277 AC: 42147 AN: 152008 Hom.: 5960 Cov.: 32 AF XY: 0.281 AC XY: 20862 AN XY: 74284

African (AFR) AF: 0.208 AC: 8622 AN: 41498

American (AMR) AF: 0.284 AC: 4324 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 954 AN: 3470

East Asian (EAS) AF: 0.464 AC: 2393 AN: 5158

South Asian (SAS) AF: 0.289 AC: 1394 AN: 4828

European-Finnish (FIN) AF: 0.349 AC: 3674 AN: 10542

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19614 AN: 67952

Other (OTH) AF: 0.294 AC: 619 AN: 2104

Alfa AF: 0.271 Hom.: 717

Bravo AF: 0.275

Asia WGS AF: 0.348 AC: 1205 AN: 3456

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinitis pigmentosa 25 Benign:1

Jul 01, 2021

Genome-Nilou Lab

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	-0.86
CADD	Benign	0.36
DANN	Benign	0.71
PhyloP100		-0.56
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: rs36133910; hg19: chr6-65098515; COSMIC: COSV65474589;