Variant 1-203495872-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_014359.4(OPTC):c.-41-93G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0142 in 698,578 control chromosomes in the GnomAD database, including 172 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 17 hom., cov: 32)

Exomes 𝑓: 0.015 ( 155 hom. )

Consequence

OPTC
NM_014359.4 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.683

Variant links:

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]

OPTC links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 1-203495872-G-A is Benign according to our data. Variant chr1-203495872-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1317895.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0105 (1604/152226) while in subpopulation SAS AF= 0.0382 (184/4816). AF 95% confidence interval is 0.0337. There are 17 homozygotes in gnomad4. There are 829 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 17 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPTC	NM_014359.4 linkuse as main transcript	c.-41-93G>A		intron_variant		ENST00000367222.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPTC	ENST00000367222.7 linkuse as main transcript	c.-41-93G>A		intron_variant		1	NM_014359.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0106

AC:

1606

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00215

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0253

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.0166

Gnomad SAS

AF:

0.0386

Gnomad FIN

AF:

0.00424

Gnomad MID

AF:

0.0446

Gnomad NFE

AF:

0.0106

Gnomad OTH

AF:

0.0153

GnomAD4 exome

AF:

0.0153

AC:

8345

AN:

546352

Hom.:

155

AF XY:

0.0168

AC XY:

4933

AN XY:

293858

show subpopulations

Gnomad4 AFR exome

AF:

0.00185

Gnomad4 AMR exome

AF:

0.0333

Gnomad4 ASJ exome

AF:

0.00923

Gnomad4 EAS exome

AF:

0.00875

Gnomad4 SAS exome

AF:

0.0427

Gnomad4 FIN exome

AF:

0.00500

Gnomad4 NFE exome

AF:

0.0108

Gnomad4 OTH exome

AF:

0.0153

GnomAD4 genome

AF:

0.0105

AC:

1604

AN:

152226

Hom.:

Cov.:

AF XY:

0.0111

AC XY:

829

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00214

Gnomad4 AMR

AF:

0.0253

Gnomad4 ASJ

AF:

0.0121

Gnomad4 EAS

AF:

0.0164

Gnomad4 SAS

AF:

0.0382

Gnomad4 FIN

AF:

0.00424

Gnomad4 NFE

AF:

0.0106

Gnomad4 OTH

AF:

0.0152

Alfa

AF:

0.00958

Hom.:

Bravo

AF:

0.0111

Asia WGS

AF:

0.0240

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 26, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.60

DANN

Benign

0.45

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over