6-64432761-G-T

Position:

• chr6-64432761-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001142800.2(EYS):​c.5927+3413C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0251 in 151,960 control chromosomes in the GnomAD database, including 73 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 0.025 (73 hom., cov: 32)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0940

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=-0.93).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0251 (3811/151960) while in subpopulation NFE AF= 0.0377 (2561/67886). AF 95% confidence interval is 0.0365. There are 73 homozygotes in gnomad4. There are 1815 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 73 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EYS	NM_001142800.2	c.5927+3413C>A		intron_variant		ENST00000503581.6
EYS	NM_001292009.2	c.5927+3413C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EYS	ENST00000503581.6	c.5927+3413C>A		intron_variant		5	NM_001142800.2	A2
EYS	ENST00000370621.7	c.5927+3413C>A		intron_variant		1		P2

Frequencies

GnomAD3 genomes AF: 0.0251 AC: 3813 AN: 151842 Hom.: 73 Cov.: 32

Gnomad AFR AF: 0.00691

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0256

Gnomad ASJ AF: 0.0228

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00539

Gnomad FIN AF: 0.0384

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0377

Gnomad OTH AF: 0.0264

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

GnomAD4 genome AF: 0.0251 AC: 3811 AN: 151960 Hom.: 73 Cov.: 32 AF XY: 0.0244 AC XY: 1815 AN XY: 74298

Gnomad4 AFR AF: 0.00689

Gnomad4 AMR AF: 0.0255

Gnomad4 ASJ AF: 0.0228

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00539

Gnomad4 FIN AF: 0.0384

Gnomad4 NFE AF: 0.0377

Gnomad4 OTH AF: 0.0261

Alfa AF: 0.0284 Hom.: 11

Bravo AF: 0.0246

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.49
DANN	Benign	0.36

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: rs17479806; hg19: chr6-65142654;