rs8123716

chr20-25082079-C-A

Variant summary

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

The NM_014588.6(VSX1):c.18G>T(p.Ser6=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0835 in 1,538,440 control chromosomes in the GnomAD database, including 6,213 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 434 hom., cov: 33)

Exomes 𝑓: 0.086 ( 5779 hom. )

Consequence

VSX1
NM_014588.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0370

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=-0.52).

BP6

Variant 20-25082079-C-A is Benign according to our data. Variant chr20-25082079-C-A is described in ClinVar as [Benign]. Clinvar id is 260423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.037 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0968 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.18G>T	p.Ser6=	synonymous_variant	1/5	ENST00000376709.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VSX1	ENST00000376709.9 linkuse as main transcript	c.18G>T	p.Ser6=	synonymous_variant	1/5	1	NM_014588.6	P1	Q9NZR4-1

Frequencies

GnomAD3 genomes

AF:

0.0634

AC:

9655

AN:

152184

Hom.:

434

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0161

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.0543

Gnomad ASJ

AF:

0.0841

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0174

Gnomad FIN

AF:

0.0863

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0988

Gnomad OTH

AF:

0.0544

GnomAD3 exomes

AF:

0.0576

AC:

7685

AN:

133482

Hom.:

324

AF XY:

0.0559

AC XY:

4080

AN XY:

73018

show subpopulations

Gnomad AFR exome

AF:

0.0143

Gnomad AMR exome

AF:

0.0385

Gnomad ASJ exome

AF:

0.0823

Gnomad EAS exome

AF:

0.0000902

Gnomad SAS exome

AF:

0.0163

Gnomad FIN exome

AF:

0.0946

Gnomad NFE exome

AF:

0.0953

Gnomad OTH exome

AF:

0.0593

GnomAD4 exome

AF:

0.0857

AC:

118833

AN:

1386140

Hom.:

5779

Cov.:

AF XY:

0.0836

AC XY:

57231

AN XY:

684290

show subpopulations

Gnomad4 AFR exome

AF:

0.0129

Gnomad4 AMR exome

AF:

0.0408

Gnomad4 ASJ exome

AF:

0.0788

Gnomad4 EAS exome

AF:

0.000138

Gnomad4 SAS exome

AF:

0.0178

Gnomad4 FIN exome

AF:

0.0968

Gnomad4 NFE exome

AF:

0.0980

Gnomad4 OTH exome

AF:

0.0755

GnomAD4 genome

AF:

0.0634

AC:

9651

AN:

152300

Hom.:

434

Cov.:

AF XY:

0.0618

AC XY:

4603

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0160

Gnomad4 AMR

AF:

0.0542

Gnomad4 ASJ

AF:

0.0841

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0174

Gnomad4 FIN

AF:

0.0863

Gnomad4 NFE

AF:

0.0988

Gnomad4 OTH

AF:

0.0539

Alfa

AF:

0.0866

Hom.:

181

Bravo

AF:

0.0584

Asia WGS

AF:

0.00953

AC:

AN:

3478

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 26, 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

-0.52

Cadd

Benign

5.6

Dann

Benign

0.82

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