chr6-63814258-G-T

Variant names:

• chr6-63814258-G-T
• rs6921058
• NM_001142800.2:c.7229-7886C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000503581.6(EYS):​c.7229-7886C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 151,978 control chromosomes in the GnomAD database, including 21,242 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (21242 hom., cov: 32)
• Consequence: EYS ENST00000503581.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860
• Publications: 2 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]

SCAT8 (HGNC:40967): (S-phase cancer associated transcript 8)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000503581.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	NM_001142800.2	MANE Select	c.7229-7886C>A		intron	N/A	NP_001136272.1
	EYS	NM_001292009.2		c.7229-7886C>A		intron	N/A	NP_001278938.1
	SCAT8	NR_157848.1		n.52-6982G>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	ENST00000503581.6	TSL:5 MANE Select	c.7229-7886C>A		intron	N/A	ENSP00000424243.1
	EYS	ENST00000370621.7	TSL:1	c.7229-7886C>A		intron	N/A	ENSP00000359655.3
	EYS	ENST00000398580.3	TSL:5	c.542-7886C>A		intron	N/A	ENSP00000381585.3

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76857 AN: 151860 Hom.: 21193 Cov.: 32

Gnomad AFR AF: 0.727

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.470

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.506 AC: 76963 AN: 151978 Hom.: 21242 Cov.: 32 AF XY: 0.506 AC XY: 37608 AN XY: 74258

African (AFR) AF: 0.728 AC: 30184 AN: 41480

American (AMR) AF: 0.530 AC: 8092 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 1603 AN: 3470

East Asian (EAS) AF: 0.446 AC: 2300 AN: 5152

South Asian (SAS) AF: 0.533 AC: 2572 AN: 4822

European-Finnish (FIN) AF: 0.333 AC: 3499 AN: 10518

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.400 AC: 27215 AN: 67956

Other (OTH) AF: 0.466 AC: 983 AN: 2110

Alfa AF: 0.353 Hom.: 1249

Bravo AF: 0.531

Asia WGS AF: 0.462 AC: 1604 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.72
DANN	Benign	0.22
PhyloP100		0.086
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: rs6921058; hg19: chr6-64524151;