1-203496268-T-C

Variant names:

• chr1-203496268-T-C
• rs2242199
• NM_014359.4:c.231+32T>C

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.231+32T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 1,504,090 control chromosomes in the GnomAD database, including 122,013 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (10930 hom., cov: 32)
  • Exomes 𝑓: 0.40 (111083 hom.)
• Consequence: OPTC NM_014359.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.111
• Publications: 8 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=-0.86).
• BP6: Variant 1-203496268-T-C is Benign according to our data. Variant chr1-203496268-T-C is described in ClinVar as Benign. ClinVar VariationId is 1230152.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.461 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+32T>C		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.231+32T>C		intron	N/A	ENSP00000356191.2	Q9UBM4
	OPTC	ENST00000715259.1		c.231+32T>C		intron	N/A	ENSP00000520429.1	Q9UBM4
	OPTC	ENST00000448911.2	TSL:2	c.231+32T>C		intron	N/A	ENSP00000399491.2	Q5T2G3

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57069 AN: 151934 Hom.: 10931 Cov.: 32

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.550

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.352

GnomAD2 exomes AF: 0.397 AC: 97169 AN: 244740 AF XY: 0.399

Gnomad AFR exome AF: 0.310

Gnomad AMR exome AF: 0.329

Gnomad ASJ exome AF: 0.399

Gnomad EAS exome AF: 0.478

Gnomad FIN exome AF: 0.483

Gnomad NFE exome AF: 0.402

Gnomad OTH exome AF: 0.382

GnomAD4 exome AF: 0.404 AC: 545937 AN: 1352038 Hom.: 111083 Cov.: 21 AF XY: 0.403 AC XY: 273537 AN XY: 678362

African (AFR) AF: 0.308 AC: 9598 AN: 31130

American (AMR) AF: 0.331 AC: 14606 AN: 44142

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 10163 AN: 25404

East Asian (EAS) AF: 0.512 AC: 20030 AN: 39152

South Asian (SAS) AF: 0.395 AC: 33105 AN: 83810

European-Finnish (FIN) AF: 0.478 AC: 25294 AN: 52962

Middle Eastern (MID) AF: 0.305 AC: 1686 AN: 5536

European-Non Finnish (NFE) AF: 0.404 AC: 409077 AN: 1013056

Other (OTH) AF: 0.394 AC: 22378 AN: 56846

GnomAD4 genome AF: 0.376 AC: 57121 AN: 152052 Hom.: 10930 Cov.: 32 AF XY: 0.379 AC XY: 28191 AN XY: 74344

African (AFR) AF: 0.310 AC: 12856 AN: 41486

American (AMR) AF: 0.326 AC: 4982 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1331 AN: 3472

East Asian (EAS) AF: 0.476 AC: 2451 AN: 5144

South Asian (SAS) AF: 0.402 AC: 1936 AN: 4820

European-Finnish (FIN) AF: 0.483 AC: 5112 AN: 10594

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.399 AC: 27114 AN: 67930

Other (OTH) AF: 0.351 AC: 741 AN: 2110

Alfa AF: 0.312 Hom.: 1314

Bravo AF: 0.360

Asia WGS AF: 0.459 AC: 1599 AN: 3478

ClinVar

ClinVar submissions

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	-0.86
CADD	Benign	1.2
DANN	Benign	0.65
PhyloP100		-0.11
PromoterAI		0.0050	Neutral
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: rs2242199; hg19: chr1-203465396; COSMIC: COSV58115457; COSMIC: COSV58115457;