Genetic Variant OPTC:c.231+28T>G (chr1-203496264-T-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014359.4(OPTC):c.231+28T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0556 in 1,542,504 control chromosomes in the GnomAD database, including 3,508 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.093 ( 964 hom., cov: 32)

Exomes 𝑓: 0.052 ( 2544 hom. )

Consequence

OPTC
NM_014359.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.285

Publications

3 publications found

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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 1-203496264-T-G is Benign according to our data. Variant chr1-203496264-T-G is described in ClinVar as Benign. ClinVar VariationId is 1269950.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014359.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPTC	NM_014359.4	MANE Select	c.231+28T>G		intron	N/A	NP_055174.1	Q9UBM4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
OPTC	ENST00000367222.7	TSL:1 MANE Select	c.231+28T>G	intron	N/A	ENSP00000356191.2	Q9UBM4
OPTC	ENST00000715259.1		c.231+28T>G	intron	N/A	ENSP00000520429.1	Q9UBM4
OPTC	ENST00000448911.2	TSL:2	c.231+28T>G	intron	N/A	ENSP00000399491.2	Q5T2G3

Frequencies

GnomAD3 genomes

AF:

0.0932

AC:

14171

AN:

152050

Hom.:

965

Cov.:

show subpopulations

Gnomad AFR

AF:

0.189

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.0804

Gnomad ASJ

AF:

0.0599

Gnomad EAS

AF:

0.164

Gnomad SAS

AF:

0.0587

Gnomad FIN

AF:

0.0437

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.0451

Gnomad OTH

AF:

0.0923

GnomAD2 exomes

AF:

0.0708

AC:

17491

AN:

246960

AF XY:

0.0671

show subpopulations

Gnomad AFR exome

AF:

0.193

Gnomad AMR exome

AF:

0.0760

Gnomad ASJ exome

AF:

0.0596

Gnomad EAS exome

AF:

0.184

Gnomad FIN exome

AF:

0.0403

Gnomad NFE exome

AF:

0.0453

Gnomad OTH exome

AF:

0.0629

GnomAD4 exome

AF:

0.0515

AC:

71642

AN:

1390336

Hom.:

2544

Cov.:

AF XY:

0.0508

AC XY:

35377

AN XY:

695926

show subpopulations

African (AFR)

AF:

0.195

AC:

6197

AN:

31856

American (AMR)

AF:

0.0738

AC:

3281

AN:

44452

Ashkenazi Jewish (ASJ)

AF:

0.0601

AC:

1541

AN:

25650

East Asian (EAS)

AF:

0.143

AC:

5628

AN:

39348

South Asian (SAS)

AF:

0.0516

AC:

4368

AN:

84680

European-Finnish (FIN)

AF:

0.0412

AC:

2192

AN:

53142

Middle Eastern (MID)

AF:

0.0879

AC:

494

AN:

5618

European-Non Finnish (NFE)

AF:

0.0424

AC:

44381

AN:

1047504

Other (OTH)

AF:

0.0613

AC:

3560

AN:

58086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

3561

7121

10682

14242

17803

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1782

3564

5346

7128

8910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0931

AC:

14172

AN:

152168

Hom.:

964

Cov.:

AF XY:

0.0924

AC XY:

6872

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.189

AC:

7821

AN:

41484

American (AMR)

AF:

0.0802

AC:

1227

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0599

AC:

208

AN:

3470

East Asian (EAS)

AF:

0.164

AC:

846

AN:

5156

South Asian (SAS)

AF:

0.0585

AC:

282

AN:

4818

European-Finnish (FIN)

AF:

0.0437

AC:

464

AN:

10616

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0452

AC:

3071

AN:

68012

Other (OTH)

AF:

0.0899

AC:

190

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

650

1299

1949

2598

3248

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

296

444

592

740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0685

Hom.:

Bravo

AF:

0.101

Asia WGS

AF:

0.0900

AC:

314

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.6

(source)

DANN

Benign

0.26

PhyloP100

-0.28

PromoterAI

-0.018

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over