1-203495804-C-T

Position:

• chr1-203495804-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014359.4(OPTC):​c.-41-161C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0446 in 152,156 control chromosomes in the GnomAD database, including 212 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Genomes: 𝑓 0.045 (212 hom., cov: 32)
• Consequence: OPTC NM_014359.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.279

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-203495804-C-T is Benign according to our data. Variant chr1-203495804-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1317559.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPTC	NM_014359.4	c.-41-161C>T		intron_variant		ENST00000367222.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPTC	ENST00000367222.7	c.-41-161C>T		intron_variant		1	NM_014359.4	P1

Frequencies

GnomAD3 genomes AF: 0.0447 AC: 6792 AN: 152036 Hom.: 213 Cov.: 32

Gnomad AFR AF: 0.0201

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0628

Gnomad ASJ AF: 0.0591

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.0549

Gnomad FIN AF: 0.0439

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0447

Gnomad OTH AF: 0.0523

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

GnomAD4 genome AF: 0.0446 AC: 6785 AN: 152156 Hom.: 212 Cov.: 32 AF XY: 0.0462 AC XY: 3438 AN XY: 74386

Gnomad4 AFR AF: 0.0201

Gnomad4 AMR AF: 0.0627

Gnomad4 ASJ AF: 0.0591

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.0550

Gnomad4 FIN AF: 0.0439

Gnomad4 NFE AF: 0.0447

Gnomad4 OTH AF: 0.0507

Alfa AF: 0.0259 Hom.: 19

Bravo AF: 0.0455

Asia WGS AF: 0.0800 AC: 278 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 20, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.1
DANN	Benign	0.77

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: rs2242200; hg19: chr1-203464932;