rs10944484

Positions:

• chr6-64357511-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142800.2(EYS):​c.6078+31179G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 151,560 control chromosomes in the GnomAD database, including 2,358 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 0.16 (2358 hom., cov: 34)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.323

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EYS	NM_001142800.2	c.6078+31179G>T		intron_variant		ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.6078+31179G>T		intron_variant			NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.6078+31179G>T		intron_variant		5	NM_001142800.2	ENSP00000424243	A2
EYS	ENST00000370621.7	c.6078+31179G>T		intron_variant		1		ENSP00000359655	P2

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23826 AN: 151442 Hom.: 2356 Cov.: 34

Gnomad AFR AF: 0.0394

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.0883

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.157 AC: 23825 AN: 151560 Hom.: 2358 Cov.: 34 AF XY: 0.157 AC XY: 11639 AN XY: 74064

Gnomad4 AFR AF: 0.0393

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.0881

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.176

Alfa AF: 0.191 Hom.: 3921

Bravo AF: 0.163

Asia WGS AF: 0.167 AC: 579 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.7
DANN	Benign	0.55

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

Publications

LitVar

Other links and lift over

dbSNP: rs10944484; hg19: chr6-65067404;