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. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.863-24_863-22dupTTT		intron_variant	Intron 5 of 42	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.863-24_863-22dupTTT		intron_variant	Intron 5 of 43		NP_001278938.1
EYS	NM_001142801.2	c.863-24_863-22dupTTT		intron_variant	Intron 5 of 11		NP_001136273.1
EYS	NM_198283.2	c.863-24_863-22dupTTT		intron_variant	Intron 4 of 9		NP_938024.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.863-22_863-21insTTT		intron_variant	Intron 5 of 42	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.863-22_863-21insTTT		intron_variant	Intron 5 of 43	1		ENSP00000359655.3
EYS	ENST00000393380.6	c.863-22_863-21insTTT		intron_variant	Intron 5 of 11	1		ENSP00000377042.2
EYS	ENST00000342421.9	c.863-22_863-21insTTT		intron_variant	Intron 3 of 8	1		ENSP00000341818.5

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

GnomAD3 exomes AF: 0.204 AC: 41232 AN: 202572 Hom.: 1585 AF XY: 0.204 AC XY: 22603 AN XY: 110630

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 SAS exome AF: 0.149

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

Gnomad4 AFR exome AF: 0.0575

Gnomad4 AMR exome AF: 0.214

Gnomad4 ASJ exome AF: 0.224

Gnomad4 EAS exome AF: 0.171

Gnomad4 SAS exome AF: 0.148

Gnomad4 FIN exome AF: 0.247

Gnomad4 NFE exome AF: 0.239

Gnomad4 OTH exome AF: 0.215

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

Gnomad4 AFR AF: 0.0615

Gnomad4 AMR AF: 0.264

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.189

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.267

Gnomad4 OTH AF: 0.236

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 11, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinitis pigmentosa 25 Benign:1

Sep 27, 2019

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs34154043; hg19: chr6-66115281;