rs587278

Variant names:

• chr6-64388875-A-G
• rs587278
• NM_001142800.2:c.5928-35T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-64388875-A-G
• chr6-64388875-A-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.5928-35T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 1,367,990 control chromosomes in the GnomAD database, including 339,400 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.72 (39780 hom., cov: 32)
  • Exomes 𝑓: 0.70 (299620 hom.)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.363
• Publications: 10 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: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 1 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 6-64388875-A-G is Benign according to our data. Variant chr6-64388875-A-G is described in ClinVar as Benign. ClinVar VariationId is 1175358.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.5928-35T>C		intron_variant	Intron 28 of 42	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.5928-35T>C		intron_variant	Intron 28 of 43		NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.5928-35T>C		intron_variant	Intron 28 of 42	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.5928-35T>C		intron_variant	Intron 28 of 43	1		ENSP00000359655.3
ENSG00000232120	ENST00000424274.1	n.267+9163A>G		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.722 AC: 109700 AN: 151860 Hom.: 39744 Cov.: 32

Gnomad AFR AF: 0.792

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.716

Gnomad ASJ AF: 0.725

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.712

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.711

Gnomad OTH AF: 0.704

GnomAD2 exomes AF: 0.697 AC: 63755 AN: 91408 AF XY: 0.696

Gnomad AFR exome AF: 0.788

Gnomad AMR exome AF: 0.729

Gnomad ASJ exome AF: 0.726

Gnomad EAS exome AF: 0.514

Gnomad FIN exome AF: 0.658

Gnomad NFE exome AF: 0.711

Gnomad OTH exome AF: 0.679

GnomAD4 exome AF: 0.702 AC: 853163 AN: 1216012 Hom.: 299620 Cov.: 17 AF XY: 0.702 AC XY: 418616 AN XY: 596434

African (AFR) AF: 0.794 AC: 19866 AN: 25014

American (AMR) AF: 0.718 AC: 13623 AN: 18974

Ashkenazi Jewish (ASJ) AF: 0.714 AC: 15377 AN: 21532

East Asian (EAS) AF: 0.541 AC: 16385 AN: 30312

South Asian (SAS) AF: 0.709 AC: 38376 AN: 54112

European-Finnish (FIN) AF: 0.653 AC: 30125 AN: 46156

Middle Eastern (MID) AF: 0.709 AC: 3680 AN: 5188

European-Non Finnish (NFE) AF: 0.706 AC: 680496 AN: 964184

Other (OTH) AF: 0.697 AC: 35235 AN: 50540

GnomAD4 genome AF: 0.722 AC: 109792 AN: 151978 Hom.: 39780 Cov.: 32 AF XY: 0.719 AC XY: 53388 AN XY: 74294

African (AFR) AF: 0.792 AC: 32843 AN: 41476

American (AMR) AF: 0.716 AC: 10939 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.725 AC: 2513 AN: 3466

East Asian (EAS) AF: 0.535 AC: 2761 AN: 5158

South Asian (SAS) AF: 0.711 AC: 3433 AN: 4828

European-Finnish (FIN) AF: 0.650 AC: 6853 AN: 10540

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.711 AC: 48313 AN: 67926

Other (OTH) AF: 0.707 AC: 1488 AN: 2106

Alfa AF: 0.721 Hom.: 8406

Bravo AF: 0.725

Asia WGS AF: 0.650 AC: 2257 AN: 3472

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	-0.91
CADD	Benign	7.4
DANN	Benign	0.34
PhyloP100		0.36
BranchPoint Hunter		1.0
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: rs587278; hg19: chr6-65098768;