6-64357689-A-G

Variant names:

• chr6-64357689-A-G
• rs626316
• NM_001142800.2:c.6078+31001T>C

Variant summary

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

The NM_001142800.2(EYS):​c.6078+31001T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.753 in 151,406 control chromosomes in the GnomAD database, including 43,585 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 0.75 (43585 hom., cov: 32)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.849

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.6078+31001T>C		intron_variant	Intron 29 of 42	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.6078+31001T>C		intron_variant	Intron 29 of 43		NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.6078+31001T>C		intron_variant	Intron 29 of 42	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.6078+31001T>C		intron_variant	Intron 29 of 43	1		ENSP00000359655.3

Frequencies

GnomAD3 genomes AF: 0.753 AC: 113953 AN: 151288 Hom.: 43530 Cov.: 32

Gnomad AFR AF: 0.893

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.722

Gnomad ASJ AF: 0.726

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.727

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.711

Gnomad OTH AF: 0.725

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

GnomAD4 genome AF: 0.753 AC: 114067 AN: 151406 Hom.: 43585 Cov.: 32 AF XY: 0.750 AC XY: 55458 AN XY: 73968

Gnomad4 AFR AF: 0.893

Gnomad4 AMR AF: 0.721

Gnomad4 ASJ AF: 0.726

Gnomad4 EAS AF: 0.566

Gnomad4 SAS AF: 0.727

Gnomad4 FIN AF: 0.663

Gnomad4 NFE AF: 0.711

Gnomad4 OTH AF: 0.727

Alfa AF: 0.736 Hom.: 4853

Bravo AF: 0.757

Asia WGS AF: 0.678 AC: 2357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.13
DANN	Benign	0.48

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: rs626316; hg19: chr6-65067582;