1-203497062-C-T

Variant names:

Variant summary

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

The NM_014359.4(OPTC):c.317C>T(p.Thr106Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00141 in 1,614,118 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 47 hom. )

Consequence

OPTC
NM_014359.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.11

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030830204).

BP6

Variant 1-203497062-C-T is Benign according to our data. Variant chr1-203497062-C-T is described in ClinVar as [Benign]. Clinvar id is 770499.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00206 (313/152282) while in subpopulation AMR AF= 0.0171 (261/15300). AF 95% confidence interval is 0.0154. There are 4 homozygotes in gnomad4. There are 164 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPTC	NM_014359.4 link	c.317C>T	p.Thr106Met	missense_variant	Exon 3 of 8	ENST00000367222.7	NP_055174.1	Q9UBM4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPTC	ENST00000367222.7 link	c.317C>T	p.Thr106Met	missense_variant	Exon 3 of 8	1	NM_014359.4	ENSP00000356191.2		Q9UBM4
OPTC	ENST00000448911.1 link	c.317C>T	p.Thr106Met	missense_variant	Exon 2 of 4	2		ENSP00000399491.2		Q5T2G3

Frequencies

GnomAD3 genomes

AF:

0.00206

AC:

313

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0171

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00288

GnomAD3 exomes

AF:

0.00600

AC:

1509

AN:

251402

Hom.:

AF XY:

0.00451

AC XY:

613

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.0408

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00114

Gnomad SAS exome

AF:

0.00144

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.00342

GnomAD4 exome

AF:

0.00135

AC:

1967

AN:

1461836

Hom.:

Cov.:

AF XY:

0.00111

AC XY:

808

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.000418

Gnomad4 AMR exome

AF:

0.0382

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000831

Gnomad4 SAS exome

AF:

0.00119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000252

Gnomad4 OTH exome

AF:

0.00127

GnomAD4 genome

AF:

0.00206

AC:

313

AN:

152282

Hom.:

Cov.:

AF XY:

0.00220

AC XY:

164

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.000602

Gnomad4 AMR

AF:

0.0171

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00285

Alfa

AF:

0.000326

Hom.:

Bravo

AF:

0.00360

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00453

AC:

550

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 28, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

OPTC-related disorder

Benign:1

May 22, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.53

CADD

Benign

2.0

DANN

Uncertain

0.98

DEOGEN2

Benign

0.032

T;T

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.38

T;T

MetaRNN

Benign

0.0031

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;.

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.040

Sift

Benign

0.19

T;T

Sift4G

Benign

0.072

T;D

Polyphen

0.53

P;.

Vest4

0.11

MVP

0.49

MPC

0.098

ClinPred

0.0065

GERP RS

1.1

Varity_R

0.017

gMVP

0.40

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