chr6-65343942-T-G

Variant names:

• chr6-65343942-T-G
• rs1502963
• NM_001142800.2:c.1599+96A>C

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.1599+96A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.999 in 1,048,414 control chromosomes in the GnomAD database, including 522,841 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.99 (74965 hom., cov: 32)
  • Exomes 𝑓: 1.0 (447876 hom.)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.669
• Publications: 4 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 6-65343942-T-G is Benign according to our data. Variant chr6-65343942-T-G is described in ClinVar as Benign. ClinVar VariationId is 1175350.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142800.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	NM_001142800.2	MANE Select	c.1599+96A>C		intron	N/A	NP_001136272.1
	EYS	NM_001292009.2		c.1599+96A>C		intron	N/A	NP_001278938.1
	EYS	NM_001142801.2		c.1599+96A>C		intron	N/A	NP_001136273.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	ENST00000503581.6	TSL:5 MANE Select	c.1599+96A>C		intron	N/A	ENSP00000424243.1
	EYS	ENST00000370621.7	TSL:1	c.1599+96A>C		intron	N/A	ENSP00000359655.3
	EYS	ENST00000393380.6	TSL:1	c.1599+96A>C		intron	N/A	ENSP00000377042.2

Frequencies

GnomAD3 genomes AF: 0.995 AC: 150633 AN: 151464 Hom.: 74909 Cov.: 32

Gnomad AFR AF: 0.981

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.997

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.994

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.998

GnomAD4 exome AF: 0.999 AC: 896282 AN: 896832 Hom.: 447876 AF XY: 1.00 AC XY: 469769 AN XY: 469974

African (AFR) AF: 0.981 AC: 21021 AN: 21424

American (AMR) AF: 0.998 AC: 40358 AN: 40420

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 21768 AN: 21768

East Asian (EAS) AF: 1.00 AC: 36690 AN: 36690

South Asian (SAS) AF: 1.00 AC: 72056 AN: 72058

European-Finnish (FIN) AF: 1.00 AC: 51333 AN: 51334

Middle Eastern (MID) AF: 1.00 AC: 2979 AN: 2980

European-Non Finnish (NFE) AF: 1.00 AC: 608937 AN: 608946

Other (OTH) AF: 0.998 AC: 41140 AN: 41212

GnomAD4 genome AF: 0.994 AC: 150748 AN: 151582 Hom.: 74965 Cov.: 32 AF XY: 0.995 AC XY: 73706 AN XY: 74110

African (AFR) AF: 0.981 AC: 40672 AN: 41448

American (AMR) AF: 0.997 AC: 15089 AN: 15140

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3462 AN: 3462

East Asian (EAS) AF: 1.00 AC: 5130 AN: 5130

South Asian (SAS) AF: 1.00 AC: 4822 AN: 4822

European-Finnish (FIN) AF: 1.00 AC: 10596 AN: 10596

Middle Eastern (MID) AF: 0.993 AC: 292 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 67673 AN: 67674

Other (OTH) AF: 0.998 AC: 2100 AN: 2104

Alfa AF: 0.997 Hom.: 8613

Bravo AF: 0.994

Asia WGS AF: 0.999 AC: 3466 AN: 3468

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.40
DANN	Benign	0.69
PhyloP100		-0.67
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: rs1502963; hg19: chr6-66053835;