1-203495639-C-T

Position:

• chr1-203495639-C-T

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.-41-326C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,202 control chromosomes in the GnomAD database, including 1,781 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (1781 hom., cov: 32)
• Consequence: OPTC NM_014359.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.929

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=-0.9).
• BP6: Variant 1-203495639-C-T is Benign according to our data. Variant chr1-203495639-C-T is described in ClinVar as [Benign]. Clinvar id is 1235334.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPTC	NM_014359.4	c.-41-326C>T		intron_variant		ENST00000367222.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPTC	ENST00000367222.7	c.-41-326C>T		intron_variant		1	NM_014359.4	P1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22002 AN: 152084 Hom.: 1782 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.0866

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.145 AC: 22025 AN: 152202 Hom.: 1781 Cov.: 32 AF XY: 0.149 AC XY: 11108 AN XY: 74408

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.0864

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.313

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.130

Alfa AF: 0.133 Hom.: 280

Bravo AF: 0.136

Asia WGS AF: 0.225 AC: 782 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.21
DANN	Benign	0.76

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: rs4971245; hg19: chr1-203464767;