1-203496442-C-G

Position:

• chr1-203496442-C-G

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.231+206C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 152,004 control chromosomes in the GnomAD database, including 24,145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.56 (24145 hom., cov: 31)
• Consequence: OPTC NM_014359.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.317

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=-0.92).
• BP6: Variant 1-203496442-C-G is Benign according to our data. Variant chr1-203496442-C-G is described in ClinVar as [Benign]. Clinvar id is 1271727.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPTC	NM_014359.4	c.231+206C>G		intron_variant		ENST00000367222.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPTC	ENST00000367222.7	c.231+206C>G		intron_variant		1	NM_014359.4	P1
OPTC	ENST00000448911.1	c.231+206C>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84515 AN: 151886 Hom.: 24104 Cov.: 31

Gnomad AFR AF: 0.675

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.768

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.471

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.520

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

GnomAD4 genome AF: 0.557 AC: 84619 AN: 152004 Hom.: 24145 Cov.: 31 AF XY: 0.562 AC XY: 41712 AN XY: 74280

Gnomad4 AFR AF: 0.675

Gnomad4 AMR AF: 0.556

Gnomad4 ASJ AF: 0.464

Gnomad4 EAS AF: 0.768

Gnomad4 SAS AF: 0.525

Gnomad4 FIN AF: 0.544

Gnomad4 NFE AF: 0.479

Gnomad4 OTH AF: 0.517

Alfa AF: 0.527 Hom.: 2648

Bravo AF: 0.564

Asia WGS AF: 0.646 AC: 2249 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.98
DANN	Benign	0.27

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: rs2242198; hg19: chr1-203465570;