chr1-203497221-G-A

Position:

• chr1-203497221-G-A

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.370+106G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0607 in 1,196,120 control chromosomes in the GnomAD database, including 3,243 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.097 (1101 hom., cov: 32)
  • Exomes 𝑓: 0.055 (2142 hom.)
• Consequence: OPTC NM_014359.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.249

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=-0.88).
• BP6: Variant 1-203497221-G-A is Benign according to our data. Variant chr1-203497221-G-A is described in ClinVar as [Benign]. Clinvar id is 1243829.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPTC	NM_014359.4	c.370+106G>A		intron_variant		ENST00000367222.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPTC	ENST00000367222.7	c.370+106G>A		intron_variant		1	NM_014359.4	P1
OPTC	ENST00000448911.1	c.370+106G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0974 AC: 14803 AN: 152048 Hom.: 1102 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0804

Gnomad ASJ AF: 0.0599

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.0586

Gnomad FIN AF: 0.0408

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.0450

Gnomad OTH AF: 0.0934

GnomAD4 exome AF: 0.0554 AC: 57858 AN: 1043954 Hom.: 2142 AF XY: 0.0543 AC XY: 28886 AN XY: 532038

Gnomad4 AFR exome AF: 0.215

Gnomad4 AMR exome AF: 0.0742

Gnomad4 ASJ exome AF: 0.0608

Gnomad4 EAS exome AF: 0.139

Gnomad4 SAS exome AF: 0.0524

Gnomad4 FIN exome AF: 0.0390

Gnomad4 NFE exome AF: 0.0455

Gnomad4 OTH exome AF: 0.0662

GnomAD4 genome AF: 0.0973 AC: 14805 AN: 152166 Hom.: 1101 Cov.: 32 AF XY: 0.0969 AC XY: 7209 AN XY: 74394

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.0803

Gnomad4 ASJ AF: 0.0599

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.0584

Gnomad4 FIN AF: 0.0408

Gnomad4 NFE AF: 0.0450

Gnomad4 OTH AF: 0.0910

Alfa AF: 0.0753 Hom.: 159

Bravo AF: 0.106

Asia WGS AF: 0.0900 AC: 314 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	-0.88
CADD	Benign	0.96
DANN	Benign	0.58

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: rs2306152; hg19: chr1-203466349;