rs12480307

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_014588.6(VSX1):c.546A>G(p.Ala182=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 1,613,882 control chromosomes in the GnomAD database, including 51,842 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 7407 hom., cov: 32)

Exomes 𝑓: 0.24 ( 44435 hom. )

Consequence

VSX1
NM_014588.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.59

Variant links:

Genes affected

VSX1 (HGNC:12723): (visual system homeobox 1) The protein encoded by this gene contains a paired-like homeodomain and binds to the core of the locus control region of the red/green visual pigment gene cluster. The encoded protein may regulate expression of the cone opsin genes early in development. Mutations in this gene can cause posterior polymorphous corneal dystrophy and keratoconus. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

VSX1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 20-25078910-T-C is Benign according to our data. Variant chr20-25078910-T-C is described in ClinVar as [Benign]. Clinvar id is 100940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-25078910-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.59 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VSX1	NM_014588.6 linkuse as main transcript	c.546A>G	p.Ala182=	synonymous_variant	3/5	ENST00000376709.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VSX1	ENST00000376709.9 linkuse as main transcript	c.546A>G	p.Ala182=	synonymous_variant	3/5	1	NM_014588.6	P1	Q9NZR4-1

Frequencies

GnomAD3 genomes

AF:

0.291

AC:

44251

AN:

151910

Hom.:

7383

Cov.:

show subpopulations

Gnomad AFR

AF:

0.439

Gnomad AMI

AF:

0.227

Gnomad AMR

AF:

0.338

Gnomad ASJ

AF:

0.324

Gnomad EAS

AF:

0.0191

Gnomad SAS

AF:

0.299

Gnomad FIN

AF:

0.203

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.224

Gnomad OTH

AF:

0.285

GnomAD3 exomes

AF:

0.259

AC:

65077

AN:

251480

Hom.:

10142

AF XY:

0.252

AC XY:

34218

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.449

Gnomad AMR exome

AF:

0.428

Gnomad ASJ exome

AF:

0.313

Gnomad EAS exome

AF:

0.0129

Gnomad SAS exome

AF:

0.288

Gnomad FIN exome

AF:

0.194

Gnomad NFE exome

AF:

0.220

Gnomad OTH exome

AF:

0.249

GnomAD4 exome

AF:

0.237

AC:

346964

AN:

1461854

Hom.:

44435

Cov.:

AF XY:

0.237

AC XY:

172500

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.451

Gnomad4 AMR exome

AF:

0.412

Gnomad4 ASJ exome

AF:

0.315

Gnomad4 EAS exome

AF:

0.00892

Gnomad4 SAS exome

AF:

0.289

Gnomad4 FIN exome

AF:

0.192

Gnomad4 NFE exome

AF:

0.228

Gnomad4 OTH exome

AF:

0.242

GnomAD4 genome

AF:

0.292

AC:

44324

AN:

152028

Hom.:

7407

Cov.:

AF XY:

0.288

AC XY:

21422

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.440

Gnomad4 AMR

AF:

0.339

Gnomad4 ASJ

AF:

0.324

Gnomad4 EAS

AF:

0.0184

Gnomad4 SAS

AF:

0.299

Gnomad4 FIN

AF:

0.203

Gnomad4 NFE

AF:

0.224

Gnomad4 OTH

AF:

0.280

Alfa

AF:

0.263

Hom.:

3691

Bravo

AF:

0.308

Asia WGS

AF:

0.161

AC:

563

AN:

3478

EpiCase

AF:

0.233

EpiControl

AF:

0.236

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Polymorphous corneal dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

Cadd

Benign

0.23

Dann

Benign

0.51

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over