NM_001142800.2:c.1600-38G>A

Variant names:

• chr6-65335184-C-T
• rs1502965
• NM_001142800.2:c.1600-38G>A

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.1600-38G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.997 in 1,387,664 control chromosomes in the GnomAD database, including 689,341 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.98 (73601 hom., cov: 32)
  • Exomes 𝑓: 1.0 (615740 hom.)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.03
• Publications: 6 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=-0.91).
• BP6: Variant 6-65335184-C-T is Benign according to our data. Variant chr6-65335184-C-T is described in ClinVar as Benign. ClinVar VariationId is 1175348.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.1600-38G>A		intron_variant	Intron 10 of 42	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.1600-38G>A		intron_variant	Intron 10 of 43		NP_001278938.1
EYS	NM_001142801.2	c.1600-38G>A		intron_variant	Intron 10 of 11		NP_001136273.1
EYS	NM_198283.2	c.1600-38G>A		intron_variant	Intron 9 of 9		NP_938024.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.1600-38G>A		intron_variant	Intron 10 of 42	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.1600-38G>A		intron_variant	Intron 10 of 43	1		ENSP00000359655.3
EYS	ENST00000393380.6	c.1600-38G>A		intron_variant	Intron 10 of 11	1		ENSP00000377042.2
EYS	ENST00000342421.9	c.1600-38G>A		intron_variant	Intron 8 of 8	1		ENSP00000341818.5

Frequencies

GnomAD3 genomes AF: 0.984 AC: 149367 AN: 151752 Hom.: 73546 Cov.: 32

Gnomad AFR AF: 0.947

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.992

Gnomad ASJ AF: 0.999

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.984

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.990

GnomAD2 exomes AF: 0.996 AC: 244317 AN: 245402 AF XY: 0.997

Gnomad AFR exome AF: 0.942

Gnomad AMR exome AF: 0.997

Gnomad ASJ exome AF: 0.998

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.998

GnomAD4 exome AF: 0.998 AC: 1233590 AN: 1235794 Hom.: 615740 Cov.: 17 AF XY: 0.999 AC XY: 626152 AN XY: 627062

African (AFR) AF: 0.944 AC: 27370 AN: 29008

American (AMR) AF: 0.996 AC: 44036 AN: 44196

Ashkenazi Jewish (ASJ) AF: 0.997 AC: 24554 AN: 24618

East Asian (EAS) AF: 1.00 AC: 38414 AN: 38414

South Asian (SAS) AF: 1.00 AC: 81711 AN: 81722

European-Finnish (FIN) AF: 1.00 AC: 49748 AN: 49748

Middle Eastern (MID) AF: 0.999 AC: 5350 AN: 5358

European-Non Finnish (NFE) AF: 1.00 AC: 909856 AN: 909950

Other (OTH) AF: 0.996 AC: 52551 AN: 52780

GnomAD4 genome AF: 0.984 AC: 149480 AN: 151870 Hom.: 73601 Cov.: 32 AF XY: 0.985 AC XY: 73103 AN XY: 74232

African (AFR) AF: 0.947 AC: 39275 AN: 41492

American (AMR) AF: 0.992 AC: 15061 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.999 AC: 3458 AN: 3462

East Asian (EAS) AF: 1.00 AC: 5128 AN: 5128

South Asian (SAS) AF: 1.00 AC: 4821 AN: 4822

European-Finnish (FIN) AF: 1.00 AC: 10630 AN: 10630

Middle Eastern (MID) AF: 0.983 AC: 289 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 67822 AN: 67838

Other (OTH) AF: 0.990 AC: 2084 AN: 2104

Alfa AF: 0.992 Hom.: 14284

Bravo AF: 0.982

Asia WGS AF: 0.997 AC: 3468 AN: 3478

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	0.29
DANN	Benign	0.78
PhyloP100		-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: rs1502965; hg19: chr6-66045077;