Variant chr20-25075765-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_014588.6(VSX1):c.*496A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0343 in 156,814 control chromosomes in the GnomAD database, including 124 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 114 hom., cov: 33)

Exomes 𝑓: 0.038 ( 10 hom. )

Consequence

VSX1
NM_014588.6 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -4.30

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 20-25075765-T-C is Benign according to our data. Variant chr20-25075765-T-C is described in ClinVar as [Benign]. Clinvar id is 337948.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0342 (5201/152172) while in subpopulation NFE AF= 0.051 (3471/68022). AF 95% confidence interval is 0.0496. There are 114 homozygotes in gnomad4. There are 2442 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 5201 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VSX1	NM_014588.6 linkuse as main transcript	c.*496A>G		3_prime_UTR_variant	5/5	ENST00000376709.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VSX1	ENST00000376709.9 linkuse as main transcript	c.*496A>G		3_prime_UTR_variant	5/5	1	NM_014588.6	P1	Q9NZR4-1

Frequencies

GnomAD3 genomes

AF:

0.0342

AC:

5204

AN:

152054

Hom.:

115

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00956

Gnomad AMI

AF:

0.0463

Gnomad AMR

AF:

0.0470

Gnomad ASJ

AF:

0.0418

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0164

Gnomad FIN

AF:

0.0218

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0511

Gnomad OTH

AF:

0.0501

GnomAD4 exome

AF:

0.0383

AC:

178

AN:

4642

Hom.:

Cov.:

AF XY:

0.0339

AC XY:

AN XY:

2362

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0364

Gnomad4 ASJ exome

AF:

0.0208

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0150

Gnomad4 FIN exome

AF:

0.0366

Gnomad4 NFE exome

AF:

0.0442

Gnomad4 OTH exome

AF:

0.0385

GnomAD4 genome

AF:

0.0342

AC:

5201

AN:

152172

Hom.:

114

Cov.:

AF XY:

0.0328

AC XY:

2442

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.00953

Gnomad4 AMR

AF:

0.0468

Gnomad4 ASJ

AF:

0.0418

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0166

Gnomad4 FIN

AF:

0.0218

Gnomad4 NFE

AF:

0.0510

Gnomad4 OTH

AF:

0.0496

Alfa

AF:

0.0416

Hom.:

Bravo

AF:

0.0353

Asia WGS

AF:

0.0100

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Polymorphous corneal dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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

-0.91

CADD

Benign

0.025

DANN

Benign

0.60

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