6-65405388-GA-GAAAA

Variant names:

• chr6-65405388-G-GAAA
• rs34154043
• NM_001142800.2:c.863-24_863-22dupTTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001142800.2(EYS):​c.863-24_863-22dupTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 1,465,574 control chromosomes in the GnomAD database, including 19,769 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (3752 hom., cov: 0)
  • Exomes 𝑓: 0.23 (16017 hom.)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.391
• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 6-65405388-G-GAAA is Benign according to our data. Variant chr6-65405388-G-GAAA is described in ClinVar as Benign. ClinVar VariationId is 1294289.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.264 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.863-24_863-22dupTTT		intron	N/A	NP_001136272.1	Q5T1H1-1
	EYS	NM_001292009.2		c.863-24_863-22dupTTT		intron	N/A	NP_001278938.1	Q5T1H1-3
	EYS	NM_001142801.2		c.863-24_863-22dupTTT		intron	N/A	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.863-22_863-21insTTT		intron	N/A	ENSP00000424243.1	Q5T1H1-1
	EYS	ENST00000370621.7	TSL:1	c.863-22_863-21insTTT		intron	N/A	ENSP00000359655.3	Q5T1H1-3
	EYS	ENST00000393380.6	TSL:1	c.863-22_863-21insTTT		intron	N/A	ENSP00000377042.2	Q5T1H1-4

Frequencies

GnomAD3 genomes AF: 0.205 AC: 30311 AN: 148014 Hom.: 3750 Cov.: 0

Gnomad AFR AF: 0.0616

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.237

GnomAD2 exomes AF: 0.204 AC: 41232 AN: 202572 AF XY: 0.204

Gnomad AFR exome AF: 0.0530

Gnomad AMR exome AF: 0.214

Gnomad ASJ exome AF: 0.225

Gnomad EAS exome AF: 0.170

Gnomad FIN exome AF: 0.242

Gnomad NFE exome AF: 0.231

Gnomad OTH exome AF: 0.219

GnomAD4 exome AF: 0.226 AC: 298144 AN: 1317460 Hom.: 16017 Cov.: 25 AF XY: 0.225 AC XY: 148108 AN XY: 658590

African (AFR) AF: 0.0575 AC: 1709 AN: 29730

American (AMR) AF: 0.214 AC: 8008 AN: 37466

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 5321 AN: 23730

East Asian (EAS) AF: 0.171 AC: 6348 AN: 37016

South Asian (SAS) AF: 0.148 AC: 11103 AN: 74894

European-Finnish (FIN) AF: 0.247 AC: 12333 AN: 50012

Middle Eastern (MID) AF: 0.219 AC: 1158 AN: 5292

European-Non Finnish (NFE) AF: 0.239 AC: 240371 AN: 1004556

Other (OTH) AF: 0.215 AC: 11793 AN: 54764

GnomAD4 genome AF: 0.205 AC: 30314 AN: 148114 Hom.: 3752 Cov.: 0 AF XY: 0.205 AC XY: 14812 AN XY: 72100

African (AFR) AF: 0.0615 AC: 2489 AN: 40474

American (AMR) AF: 0.264 AC: 3925 AN: 14844

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 819 AN: 3442

East Asian (EAS) AF: 0.189 AC: 950 AN: 5036

South Asian (SAS) AF: 0.151 AC: 711 AN: 4718

European-Finnish (FIN) AF: 0.268 AC: 2534 AN: 9446

Middle Eastern (MID) AF: 0.255 AC: 74 AN: 290

European-Non Finnish (NFE) AF: 0.267 AC: 17863 AN: 66904

Other (OTH) AF: 0.236 AC: 485 AN: 2058

Alfa AF: 0.158 Hom.: 270

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Retinitis pigmentosa 25 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.39
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs34154043; hg19: chr6-66115281; COSMIC: COSV61000691;