chr7-128775141-T-G

Variant names:

• chr7-128775141-T-G
• rs1799922
• NM_001385125.1:c.357A>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001385125.1(OPN1SW):​c.357A>C​(p.Gly119Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 1,613,548 control chromosomes in the GnomAD database, including 114,691 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7853 hom., cov: 32)
  • Exomes 𝑓: 0.37 (106838 hom.)
• Consequence: OPN1SW NM_001385125.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.513
• Publications: 26 publications found

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]

OPN1SW Gene-Disease associations (from GenCC):

• blue color blindness

  Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 7-128775141-T-G is Benign according to our data. Variant chr7-128775141-T-G is described in ClinVar as Benign. ClinVar VariationId is 1169097.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.513 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385125.1. 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
	OPN1SW	NM_001385125.1	MANE Select	c.357A>C	p.Gly119Gly	synonymous	Exon 2 of 5	NP_001372054.1	P03999

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPN1SW	ENST00000249389.3	TSL:1 MANE Select	c.357A>C	p.Gly119Gly	synonymous	Exon 2 of 5	ENSP00000249389.3	P03999

Frequencies

GnomAD3 genomes AF: 0.296 AC: 45006 AN: 152004 Hom.: 7849 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.0680

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.321

GnomAD2 exomes AF: 0.301 AC: 75425 AN: 250374 AF XY: 0.309

Gnomad AFR exome AF: 0.142

Gnomad AMR exome AF: 0.225

Gnomad ASJ exome AF: 0.372

Gnomad EAS exome AF: 0.0572

Gnomad FIN exome AF: 0.323

Gnomad NFE exome AF: 0.401

Gnomad OTH exome AF: 0.341

GnomAD4 exome AF: 0.371 AC: 542730 AN: 1461426 Hom.: 106838 Cov.: 46 AF XY: 0.368 AC XY: 267793 AN XY: 726972

African (AFR) AF: 0.141 AC: 4718 AN: 33478

American (AMR) AF: 0.229 AC: 10249 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 9786 AN: 26130

East Asian (EAS) AF: 0.0612 AC: 2431 AN: 39698

South Asian (SAS) AF: 0.210 AC: 18128 AN: 86250

European-Finnish (FIN) AF: 0.328 AC: 17502 AN: 53358

Middle Eastern (MID) AF: 0.374 AC: 2155 AN: 5768

European-Non Finnish (NFE) AF: 0.411 AC: 457024 AN: 1111676

Other (OTH) AF: 0.343 AC: 20737 AN: 60388

GnomAD4 genome AF: 0.296 AC: 45008 AN: 152122 Hom.: 7853 Cov.: 32 AF XY: 0.290 AC XY: 21595 AN XY: 74366

African (AFR) AF: 0.147 AC: 6117 AN: 41512

American (AMR) AF: 0.256 AC: 3911 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1302 AN: 3466

East Asian (EAS) AF: 0.0687 AC: 355 AN: 5164

South Asian (SAS) AF: 0.197 AC: 952 AN: 4824

European-Finnish (FIN) AF: 0.335 AC: 3549 AN: 10582

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.406 AC: 27568 AN: 67962

Other (OTH) AF: 0.317 AC: 669 AN: 2112

Alfa AF: 0.358 Hom.: 24107

Bravo AF: 0.288

Asia WGS AF: 0.127 AC: 443 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Blue color blindness (1)
-	-	1	OPN1SW-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	11
DANN	Benign	0.73
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1799922; hg19: chr7-128415195; COSMIC: COSV50821393; COSMIC: COSV50821393;