1-203495640-A-G

Position:

• chr1-203495640-A-G

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.-41-325A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,232 control chromosomes in the GnomAD database, including 2,646 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (2646 hom., cov: 32)
• Consequence: OPTC NM_014359.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.124

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=-0.84).
• BP6: Variant 1-203495640-A-G is Benign according to our data. Variant chr1-203495640-A-G is described in ClinVar as [Benign]. Clinvar id is 1252822.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPTC	NM_014359.4	c.-41-325A>G		intron_variant		ENST00000367222.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPTC	ENST00000367222.7	c.-41-325A>G		intron_variant		1	NM_014359.4	P1

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24862 AN: 152114 Hom.: 2644 Cov.: 32

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.0516

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.0963

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.0670

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.0899

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.163 AC: 24878 AN: 152232 Hom.: 2646 Cov.: 32 AF XY: 0.166 AC XY: 12355 AN XY: 74432

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.0963

Gnomad4 EAS AF: 0.308

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.0670

Gnomad4 NFE AF: 0.0899

Gnomad4 OTH AF: 0.154

Alfa AF: 0.117 Hom.: 282

Bravo AF: 0.184

Asia WGS AF: 0.209 AC: 728 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

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.1
DANN	Benign	0.62

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: rs60634125; hg19: chr1-203464768;