NM_001142800.2:c.1146T>C

Variant names:

• chr6-65402516-A-G
• rs974110
• NM_001142800.2:c.1146T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001142800.2(EYS):​c.1146T>C​(p.Asn382Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 1,529,430 control chromosomes in the GnomAD database, including 201,288 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (20917 hom., cov: 32)
  • Exomes 𝑓: 0.51 (180371 hom.)
• Consequence: EYS NM_001142800.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 0.00200
• Publications: 24 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 6-65402516-A-G is Benign according to our data. Variant chr6-65402516-A-G is described in ClinVar as Benign. ClinVar VariationId is 137262.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.002 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.531 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	NM_001142800.2	MANE Select	c.1146T>C	p.Asn382Asn	synonymous	Exon 7 of 43	NP_001136272.1	Q5T1H1-1
	EYS	NM_001292009.2		c.1146T>C	p.Asn382Asn	synonymous	Exon 7 of 44	NP_001278938.1	Q5T1H1-3
	EYS	NM_001142801.2		c.1146T>C	p.Asn382Asn	synonymous	Exon 7 of 12	NP_001136273.1	Q5T1H1-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	ENST00000503581.6	TSL:5 MANE Select	c.1146T>C	p.Asn382Asn	synonymous	Exon 7 of 43	ENSP00000424243.1	Q5T1H1-1
	EYS	ENST00000370621.7	TSL:1	c.1146T>C	p.Asn382Asn	synonymous	Exon 7 of 44	ENSP00000359655.3	Q5T1H1-3
	EYS	ENST00000393380.6	TSL:1	c.1146T>C	p.Asn382Asn	synonymous	Exon 7 of 12	ENSP00000377042.2	Q5T1H1-4

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79538 AN: 151706 Hom.: 20891 Cov.: 32

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.526

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.528

GnomAD2 exomes AF: 0.519 AC: 129770 AN: 249798 AF XY: 0.519

Gnomad AFR exome AF: 0.528

Gnomad AMR exome AF: 0.558

Gnomad ASJ exome AF: 0.578

Gnomad EAS exome AF: 0.443

Gnomad FIN exome AF: 0.536

Gnomad NFE exome AF: 0.508

Gnomad OTH exome AF: 0.524

GnomAD4 exome AF: 0.510 AC: 702437 AN: 1377606 Hom.: 180371 Cov.: 26 AF XY: 0.511 AC XY: 352198 AN XY: 689744

African (AFR) AF: 0.532 AC: 16788 AN: 31578

American (AMR) AF: 0.554 AC: 24624 AN: 44412

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 14526 AN: 25488

East Asian (EAS) AF: 0.444 AC: 17362 AN: 39092

South Asian (SAS) AF: 0.526 AC: 44250 AN: 84146

European-Finnish (FIN) AF: 0.536 AC: 28515 AN: 53222

Middle Eastern (MID) AF: 0.531 AC: 2968 AN: 5586

European-Non Finnish (NFE) AF: 0.506 AC: 524025 AN: 1036618

Other (OTH) AF: 0.511 AC: 29379 AN: 57464

GnomAD4 genome AF: 0.524 AC: 79619 AN: 151824 Hom.: 20917 Cov.: 32 AF XY: 0.529 AC XY: 39214 AN XY: 74188

African (AFR) AF: 0.536 AC: 22215 AN: 41410

American (AMR) AF: 0.538 AC: 8176 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1995 AN: 3468

East Asian (EAS) AF: 0.468 AC: 2411 AN: 5156

South Asian (SAS) AF: 0.537 AC: 2582 AN: 4810

European-Finnish (FIN) AF: 0.539 AC: 5698 AN: 10562

Middle Eastern (MID) AF: 0.514 AC: 149 AN: 290

European-Non Finnish (NFE) AF: 0.511 AC: 34689 AN: 67922

Other (OTH) AF: 0.526 AC: 1110 AN: 2112

Alfa AF: 0.516 Hom.: 34166

Bravo AF: 0.524

Asia WGS AF: 0.475 AC: 1648 AN: 3472

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	Retinitis pigmentosa (2)
-	-	2	Retinitis pigmentosa 25 (2)
-	-	1	not provided (1)
-	-	1	Retinal dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.10
DANN	Benign	0.27
PhyloP100		0.0020
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: rs974110; hg19: chr6-66112409; COSMIC: COSV60985754;