NM_001142800.2:c.-500A>G

Variant names:

• chr6-65707187-T-C
• rs1490127
• NM_001142800.2:c.-500A>G

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.-500A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,022 control chromosomes in the GnomAD database, including 3,551 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3551 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: EYS NM_001142800.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.349
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 6-65707187-T-C is Benign according to our data. Variant chr6-65707187-T-C is described in ClinVar as Benign. ClinVar VariationId is 357762.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.318 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.-500A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 43	NP_001136272.1	Q5T1H1-1
	EYS	NM_001142800.2	MANE Select	c.-500A>G		5_prime_UTR	Exon 1 of 43	NP_001136272.1	Q5T1H1-1
	EYS	NM_001292009.2		c.-500A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 44	NP_001278938.1	Q5T1H1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	ENST00000503581.6	TSL:5 MANE Select	c.-500A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 43	ENSP00000424243.1	Q5T1H1-1
	EYS	ENST00000370621.7	TSL:1	c.-500A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 44	ENSP00000359655.3	Q5T1H1-3
	EYS	ENST00000393380.6	TSL:1	c.-500A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 12	ENSP00000377042.2	Q5T1H1-4

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30966 AN: 151904 Hom.: 3545 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.0714

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.148

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.204 AC: 30997 AN: 152022 Hom.: 3551 Cov.: 32 AF XY: 0.201 AC XY: 14908 AN XY: 74318

African (AFR) AF: 0.322 AC: 13359 AN: 41434

American (AMR) AF: 0.159 AC: 2422 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 698 AN: 3464

East Asian (EAS) AF: 0.0708 AC: 366 AN: 5168

South Asian (SAS) AF: 0.149 AC: 718 AN: 4824

European-Finnish (FIN) AF: 0.161 AC: 1708 AN: 10586

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.166 AC: 11261 AN: 67960

Other (OTH) AF: 0.147 AC: 310 AN: 2110

Alfa AF: 0.190 Hom.: 1047

Bravo AF: 0.211

Asia WGS AF: 0.120 AC: 417 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	EYS-related disorder (1)
-	-	1	Retinitis pigmentosa (1)
-	-	1	Retinitis pigmentosa 25 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.2
DANN	Benign	0.75
PhyloP100		0.35
PromoterAI		0.036	Neutral
Mutation Taster		=299/1	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: rs1490127; hg19: chr6-66417080;