chr1-203495890-T-C

Position:

• chr1-203495890-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_014359.4(OPTC):​c.-41-75T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00393 in 736,380 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (39 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (18 hom.)
• Consequence: OPTC NM_014359.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.202

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 1-203495890-T-C is Benign according to our data. Variant chr1-203495890-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1317236.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 = 0.0127 (1930/152096) while in subpopulation AFR AF= 0.0439 (1823/41482). AF 95% confidence interval is 0.0423. There are 39 homozygotes in gnomad4. There are 923 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 39 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPTC	NM_014359.4	c.-41-75T>C		intron_variant		ENST00000367222.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPTC	ENST00000367222.7	c.-41-75T>C		intron_variant		1	NM_014359.4	P1

Frequencies

GnomAD3 genomes AF: 0.0127 AC: 1926 AN: 151978 Hom.: 39 Cov.: 32

Gnomad AFR AF: 0.0440

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00505

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00812

GnomAD4 exome AF: 0.00165 AC: 962 AN: 584284 Hom.: 18 AF XY: 0.00136 AC XY: 427 AN XY: 313318

Gnomad4 AFR exome AF: 0.0439

Gnomad4 AMR exome AF: 0.00269

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000272

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000605

Gnomad4 OTH exome AF: 0.00357

GnomAD4 genome AF: 0.0127 AC: 1930 AN: 152096 Hom.: 39 Cov.: 32 AF XY: 0.0124 AC XY: 923 AN XY: 74364

Gnomad4 AFR AF: 0.0439

Gnomad4 AMR AF: 0.00504

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00803

Alfa AF: 0.00908 Hom.: 4

Bravo AF: 0.0139

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	May 18, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.1
DANN	Benign	0.42

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: rs116154218; hg19: chr1-203465018;