1-203495745-G-A

Position:

• chr1-203495745-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014359.4(OPTC):​c.-41-220G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0176 in 152,284 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.018 (43 hom., cov: 32)
• Consequence: OPTC NM_014359.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0290

Genes affected

OPTC (HGNC:8158): (opticin) Opticin belongs to class III of the small leucine-rich repeat protein (SLRP) family. Members of this family are typically associated with the extracellular matrix. Opticin is present in significant quantities in the vitreous of the eye and also localizes to the cornea, iris, ciliary body, optic nerve, choroid, retina, and fetal liver. Opticin may noncovalently bind collagen fibrils and regulate fibril morphology, spacing, and organization. The opticin gene is mapped to a region of chromosome 1 that is associated with the inherited eye diseases age-related macular degeneration (AMD) and posterior column ataxia with retinosa pigmentosa (AXPC1). [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 1-203495745-G-A is Benign according to our data. Variant chr1-203495745-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1706733.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPTC	NM_014359.4	c.-41-220G>A		intron_variant		ENST00000367222.7	NP_055174.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPTC	ENST00000367222.7	c.-41-220G>A		intron_variant		1	NM_014359.4	ENSP00000356191.2

Frequencies

GnomAD3 genomes AF: 0.0176 AC: 2674 AN: 152166 Hom.: 43 Cov.: 32

Gnomad AFR AF: 0.00456

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0183

Gnomad ASJ AF: 0.0340

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0572

Gnomad FIN AF: 0.00904

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0241

Gnomad OTH AF: 0.0196

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

GnomAD4 genome AF: 0.0176 AC: 2674 AN: 152284 Hom.: 43 Cov.: 32 AF XY: 0.0171 AC XY: 1277 AN XY: 74472

Gnomad4 AFR AF: 0.00455

Gnomad4 AMR AF: 0.0183

Gnomad4 ASJ AF: 0.0340

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0576

Gnomad4 FIN AF: 0.00904

Gnomad4 NFE AF: 0.0241

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.0165 Hom.: 5

Bravo AF: 0.0168

Asia WGS AF: 0.0180 AC: 61 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.2
DANN	Benign	0.63

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: rs34000310; hg19: chr1-203464873;