rs56157240

chr20-25078745-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000376707.4(VSX1):c.711T>A(p.Pro237=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 1,613,902 control chromosomes in the GnomAD database, including 51,885 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.29 (7409 hom., cov: 31)
  • Exomes 𝑓: 0.24 (44476 hom.)
• Consequence: VSX1 ENST00000376707.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.354

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=-0.354 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	c.627+84T>A		intron_variant		ENST00000376709.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VSX1	ENST00000376709.9	c.627+84T>A		intron_variant		1	NM_014588.6	P1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44275 AN: 151916 Hom.: 7384 Cov.: 31

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.0191

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.286

GnomAD3 exomes AF: 0.259 AC: 65098 AN: 251466 Hom.: 10153 AF XY: 0.252 AC XY: 34233 AN XY: 135912

Gnomad AFR exome AF: 0.449

Gnomad AMR exome AF: 0.429

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: 347089 AN: 1461868 Hom.: 44476 Cov.: 43 AF XY: 0.237 AC XY: 172565 AN XY: 727230

Gnomad4 AFR exome AF: 0.452

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: 44349 AN: 152034 Hom.: 7409 Cov.: 31 AF XY: 0.288 AC XY: 21438 AN XY: 74330

Gnomad4 AFR AF: 0.439

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.324

Gnomad4 EAS AF: 0.0184

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.282

Alfa AF: 0.254 Hom.: 1786

Bravo AF: 0.308

Asia WGS AF: 0.163 AC: 568 AN: 3478

EpiCase AF: 0.233

EpiControl AF: 0.237

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.3
Dann	Benign	0.53

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: rs56157240; hg19: chr20-25059381; COSMIC: COSV65021405; COSMIC: COSV65021405;