rs2306152

Variant names:

• chr1-203497221-G-A
• rs2306152
• NM_014359.4:c.370+106G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014359.4(OPTC):​c.370+106G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0607 in 1,196,120 control chromosomes in the GnomAD database, including 3,243 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.097 (1101 hom., cov: 32)
  • Exomes 𝑓: 0.055 (2142 hom.)
• Consequence: OPTC NM_014359.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.249
• Publications: 2 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 1-203497221-G-A is Benign according to our data. Variant chr1-203497221-G-A is described in ClinVar as Benign. ClinVar VariationId is 1243829.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.201 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.370+106G>A		intron	N/A	NP_055174.1	Q9UBM4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPTC	ENST00000367222.7	TSL:1 MANE Select	c.370+106G>A		intron	N/A	ENSP00000356191.2	Q9UBM4
	OPTC	ENST00000715259.1		c.370+106G>A		intron	N/A	ENSP00000520429.1	Q9UBM4
	OPTC	ENST00000448911.2	TSL:2	c.370+106G>A		intron	N/A	ENSP00000399491.2	Q5T2G3

Frequencies

GnomAD3 genomes AF: 0.0974 AC: 14803 AN: 152048 Hom.: 1102 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0804

Gnomad ASJ AF: 0.0599

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.0586

Gnomad FIN AF: 0.0408

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.0450

Gnomad OTH AF: 0.0934

GnomAD4 exome AF: 0.0554 AC: 57858 AN: 1043954 Hom.: 2142 AF XY: 0.0543 AC XY: 28886 AN XY: 532038

African (AFR) AF: 0.215 AC: 5405 AN: 25184

American (AMR) AF: 0.0742 AC: 2730 AN: 36786

Ashkenazi Jewish (ASJ) AF: 0.0608 AC: 1404 AN: 23074

East Asian (EAS) AF: 0.139 AC: 4850 AN: 34844

South Asian (SAS) AF: 0.0524 AC: 3846 AN: 73398

European-Finnish (FIN) AF: 0.0390 AC: 1692 AN: 43342

Middle Eastern (MID) AF: 0.0900 AC: 450 AN: 5002

European-Non Finnish (NFE) AF: 0.0455 AC: 34384 AN: 755558

Other (OTH) AF: 0.0662 AC: 3097 AN: 46766

GnomAD4 genome AF: 0.0973 AC: 14805 AN: 152166 Hom.: 1101 Cov.: 32 AF XY: 0.0969 AC XY: 7209 AN XY: 74394

African (AFR) AF: 0.205 AC: 8496 AN: 41486

American (AMR) AF: 0.0803 AC: 1227 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0599 AC: 208 AN: 3472

East Asian (EAS) AF: 0.163 AC: 841 AN: 5168

South Asian (SAS) AF: 0.0584 AC: 282 AN: 4826

European-Finnish (FIN) AF: 0.0408 AC: 433 AN: 10614

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.0450 AC: 3063 AN: 67998

Other (OTH) AF: 0.0910 AC: 192 AN: 2110

Alfa AF: 0.0770 Hom.: 265

Bravo AF: 0.106

Asia WGS AF: 0.0900 AC: 314 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.96
DANN	Benign	0.58
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2306152; hg19: chr1-203466349;