Variant 1-203497138-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.370+23G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00175 in 1,613,400 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0060 ( 11 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 15 hom. )

Consequence

OPTC
NM_014359.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.76

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=-0.93).

BP6

Variant 1-203497138-G-A is Benign according to our data. Variant chr1-203497138-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1317697.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00602 (916/152236) while in subpopulation AFR AF= 0.019 (787/41516). AF 95% confidence interval is 0.0179. There are 11 homozygotes in gnomad4. There are 439 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPTC	NM_014359.4 link	c.370+23G>A		intron_variant		ENST00000367222.7	NP_055174.1	Q9UBM4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPTC	ENST00000367222.7 link	c.370+23G>A		intron_variant		1	NM_014359.4	ENSP00000356191.2		Q9UBM4
OPTC	ENST00000448911.1 link	c.370+23G>A		intron_variant		2		ENSP00000399491.2		Q5T2G3

Frequencies

GnomAD3 genomes

AF:

0.00603

AC:

918

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0191

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00662

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000691

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00258

AC:

645

AN:

250338

Hom.:

AF XY:

0.00229

AC XY:

310

AN XY:

135446

show subpopulations

Gnomad AFR exome

AF:

0.0189

Gnomad AMR exome

AF:

0.00220

Gnomad ASJ exome

AF:

0.00667

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00416

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000522

Gnomad OTH exome

AF:

0.00164

GnomAD4 exome

AF:

0.00130

AC:

1906

AN:

1461164

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

979

AN XY:

726894

show subpopulations

Gnomad4 AFR exome

AF:

0.0182

Gnomad4 AMR exome

AF:

0.00217

Gnomad4 ASJ exome

AF:

0.00743

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00439

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000424

Gnomad4 OTH exome

AF:

0.00234

GnomAD4 genome

AF:

0.00602

AC:

916

AN:

152236

Hom.:

Cov.:

AF XY:

0.00590

AC XY:

439

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0190

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00662

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00394

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000691

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00146

Hom.:

Bravo

AF:

0.00661

Asia WGS

AF:

0.00260

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 05, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.13

DANN

Benign

0.70

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