chr1-203498532-G-A

Position:

• chr1-203498532-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.371-149G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 863,938 control chromosomes in the GnomAD database, including 9,746 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1771 hom., cov: 32)
  • Exomes 𝑓: 0.14 (7975 hom.)
• Consequence: OPTC NM_014359.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.771

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=-0.87).
• BP6: Variant 1-203498532-G-A is Benign according to our data. Variant chr1-203498532-G-A is described in ClinVar as [Benign]. Clinvar id is 1225798.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPTC	NM_014359.4	c.371-149G>A		intron_variant		ENST00000367222.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPTC	ENST00000367222.7	c.371-149G>A		intron_variant		1	NM_014359.4	P1
OPTC	ENST00000448911.1	c.371-215G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21946 AN: 151964 Hom.: 1771 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.0863

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.130

GnomAD4 exome AF: 0.136 AC: 97044 AN: 711856 Hom.: 7975 AF XY: 0.136 AC XY: 51175 AN XY: 377118

Gnomad4 AFR exome AF: 0.163

Gnomad4 AMR exome AF: 0.0710

Gnomad4 ASJ exome AF: 0.174

Gnomad4 EAS exome AF: 0.331

Gnomad4 SAS exome AF: 0.138

Gnomad4 FIN exome AF: 0.215

Gnomad4 NFE exome AF: 0.118

Gnomad4 OTH exome AF: 0.136

GnomAD4 genome AF: 0.144 AC: 21969 AN: 152082 Hom.: 1771 Cov.: 32 AF XY: 0.149 AC XY: 11092 AN XY: 74338

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.0861

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.312

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.130

Alfa AF: 0.128 Hom.: 189

Bravo AF: 0.135

Asia WGS AF: 0.225 AC: 783 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	-0.87
CADD	Benign	0.85
DANN	Benign	0.41

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: rs6668135; hg19: chr1-203467660; COSMIC: COSV65867468;