7-128772564-C-A

Position:

• chr7-128772564-C-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_001385125.1(OPN1SW):​c.1014G>T​(p.Ser338Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,614,140 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0012 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (5 hom.)
• Consequence: OPN1SW NM_001385125.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.630

Genes affected

OPN1SW (HGNC:1012): (opsin 1, short wave sensitive) This gene belongs to the G-protein coupled receptor 1 family, opsin subfamily. It encodes the blue cone pigment gene which is one of three types of cone photoreceptors responsible for normal color vision. Defects in this gene are the cause of tritan color blindness (tritanopia). Affected individuals lack blue and yellow sensory mechanisms while retaining those for red and green. Defective blue vision is characteristic. [provided by RefSeq, Jul 2008]

CALU (HGNC:1458): (calumenin) The product of this gene is a calcium-binding protein localized in the endoplasmic reticulum (ER) and it is involved in such ER functions as protein folding and sorting. This protein belongs to a family of multiple EF-hand proteins (CERC) that include reticulocalbin, ERC-55, and Cab45 and the product of this gene. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Oct 2008]

CALU (HGNC:):

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 7-128772564-C-A is Benign according to our data. Variant chr7-128772564-C-A is described in ClinVar as [Benign]. Clinvar id is 1167587.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-128772564-C-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.63 with no splicing effect.
• BS2: High AC in GnomAd4 at 181 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPN1SW	NM_001385125.1	c.1014G>T	p.Ser338Ser	synonymous_variant	5/5	ENST00000249389.3	NP_001372054.1
CALU	NM_001219.5	c.*3397C>A		3_prime_UTR_variant	7/7	ENST00000249364.9	NP_001210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPN1SW	ENST00000249389.3	c.1014G>T	p.Ser338Ser	synonymous_variant	5/5	1	NM_001385125.1	ENSP00000249389.3
CALU	ENST00000249364.9	c.*3397C>A		3_prime_UTR_variant	7/7	1	NM_001219.5	ENSP00000249364.4
CALU	ENST00000542996.7	c.*3397C>A		3_prime_UTR_variant	8/8	1		ENSP00000438248.1
CALU	ENST00000449187.7	c.*3397C>A		3_prime_UTR_variant	7/7	1		ENSP00000408838.2

Frequencies

GnomAD3 genomes AF: 0.00119 AC: 181 AN: 152152 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00308

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000472

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00154

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00124 AC: 313 AN: 251462 Hom.: 1 AF XY: 0.00135 AC XY: 183 AN XY: 135908

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00119

Gnomad ASJ exome AF: 0.00278

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000915

Gnomad FIN exome AF: 0.000601

Gnomad NFE exome AF: 0.00171

Gnomad OTH exome AF: 0.000977

GnomAD4 exome AF: 0.00121 AC: 1771 AN: 1461870 Hom.: 5 Cov.: 31 AF XY: 0.00126 AC XY: 918 AN XY: 727234

Gnomad4 AFR exome AF: 0.000388

Gnomad4 AMR exome AF: 0.00121

Gnomad4 ASJ exome AF: 0.00268

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000672

Gnomad4 FIN exome AF: 0.000711

Gnomad4 NFE exome AF: 0.00124

Gnomad4 OTH exome AF: 0.00180

GnomAD4 genome AF: 0.00119 AC: 181 AN: 152270 Hom.: 2 Cov.: 32 AF XY: 0.00125 AC XY: 93 AN XY: 74448

Gnomad4 AFR AF: 0.000193

Gnomad4 AMR AF: 0.00307

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000472

Gnomad4 NFE AF: 0.00154

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00130 Hom.: 1

Bravo AF: 0.00106

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00240

EpiControl AF: 0.00261

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

OPN1SW-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 26, 2020

This variant is classified as likely 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
BayesDel_noAF	Benign	-0.37
CADD	Benign	2.1
DANN	Benign	0.77

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: rs140568559; hg19: chr7-128412618;