rs9445437

Variant names:

• chr6-64912769-G-C
• rs9445437
• NM_001142800.2:c.2382-26C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-64912769-G-C
• chr6-64912769-G-T

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.2382-26C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 1,299,052 control chromosomes in the GnomAD database, including 231,845 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.67 (35079 hom., cov: 32)
  • Exomes 𝑓: 0.58 (196766 hom.)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.680
• Publications: 7 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

ENSG00000308351 (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 6-64912769-G-C is Benign according to our data. Variant chr6-64912769-G-C is described in ClinVar as Benign. ClinVar VariationId is 1175365.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.2382-26C>G		intron_variant	Intron 15 of 42	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.2382-26C>G		intron_variant	Intron 15 of 43		NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.2382-26C>G		intron_variant	Intron 15 of 42	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.2382-26C>G		intron_variant	Intron 15 of 43	1		ENSP00000359655.3
ENSG00000308351	ENST00000833459.1	n.173-3554G>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.665 AC: 101025 AN: 151824 Hom.: 35040 Cov.: 32

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.655

GnomAD2 exomes AF: 0.592 AC: 28353 AN: 47900 AF XY: 0.587

Gnomad AFR exome AF: 0.891

Gnomad AMR exome AF: 0.619

Gnomad ASJ exome AF: 0.708

Gnomad EAS exome AF: 0.391

Gnomad FIN exome AF: 0.581

Gnomad NFE exome AF: 0.577

Gnomad OTH exome AF: 0.589

GnomAD4 exome AF: 0.582 AC: 667395 AN: 1147108 Hom.: 196766 Cov.: 20 AF XY: 0.581 AC XY: 318660 AN XY: 548664

African (AFR) AF: 0.895 AC: 21813 AN: 24366

American (AMR) AF: 0.632 AC: 8392 AN: 13270

Ashkenazi Jewish (ASJ) AF: 0.693 AC: 11030 AN: 15916

East Asian (EAS) AF: 0.437 AC: 13260 AN: 30324

South Asian (SAS) AF: 0.560 AC: 19347 AN: 34554

European-Finnish (FIN) AF: 0.578 AC: 22484 AN: 38896

Middle Eastern (MID) AF: 0.653 AC: 3084 AN: 4724

European-Non Finnish (NFE) AF: 0.575 AC: 540038 AN: 938572

Other (OTH) AF: 0.601 AC: 27947 AN: 46486

GnomAD4 genome AF: 0.665 AC: 101118 AN: 151944 Hom.: 35079 Cov.: 32 AF XY: 0.662 AC XY: 49160 AN XY: 74254

African (AFR) AF: 0.876 AC: 36367 AN: 41500

American (AMR) AF: 0.642 AC: 9787 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.699 AC: 2427 AN: 3472

East Asian (EAS) AF: 0.410 AC: 2113 AN: 5154

South Asian (SAS) AF: 0.554 AC: 2666 AN: 4812

European-Finnish (FIN) AF: 0.578 AC: 6088 AN: 10526

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.583 AC: 39602 AN: 67918

Other (OTH) AF: 0.656 AC: 1381 AN: 2106

Alfa AF: 0.503 Hom.: 1545

Bravo AF: 0.677

Asia WGS AF: 0.556 AC: 1934 AN: 3474

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	0.52
DANN	Benign	0.67
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9445437; hg19: chr6-65622662;