rs8123716

Variant names:

• chr20-25082079-C-A
• rs8123716
• NM_014588.6:c.18G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-25082079-C-A
• chr20-25082079-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_014588.6(VSX1):​c.18G>T​(p.Ser6Ser) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0370

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]

ACMG classification

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 rank	MANE	Protein	UniProt
VSX1	NM_014588.6	c.18G>T	p.Ser6Ser	synonymous_variant	Exon 1 of 5	ENST00000376709.9	NP_055403.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VSX1	ENST00000376709.9	c.18G>T	p.Ser6Ser	synonymous_variant	Exon 1 of 5	1	NM_014588.6	ENSP00000365899.3

Frequencies

GnomAD3 genomes AF: 0.0634 AC: 9655 AN: 152184 Hom.: 434 Cov.: 33

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

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.: 32 AF XY: 0.0836 AC XY: 57231 AN XY: 684290

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.: 33 AF XY: 0.0618 AC XY: 4603 AN XY: 74478

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: 33 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Polymorphous corneal dystrophy Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Other links and lift over

dbSNP: rs8123716; hg19: chr20-25062715;