rs141905571

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_021615.5(CHST6):c.465G>A(p.Arg155Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.008 in 1,612,672 control chromosomes in the GnomAD database, including 119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0069 ( 10 hom., cov: 33)

Exomes 𝑓: 0.0081 ( 109 hom. )

Consequence

CHST6
NM_021615.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0860

Publications

2 publications found

Variant links:

Genes affected

CHST6 (HGNC:6938): (carbohydrate sulfotransferase 6) The protein encoded by this gene is an enzyme that catalyzes the transfer of a sulfate group to the GlcNAc residues of keratan. Keratan sulfate helps maintain corneal transparency. Defects in this gene are a cause of macular corneal dystrophy (MCD). [provided by RefSeq, Jan 2010]

CHST6 Gene-Disease associations (from GenCC):

macular corneal dystrophy
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)

CHST6 links:

ENSG00000203472 (HGNC:):

ENSG00000203472 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 16-75479364-C-T is Benign according to our data. Variant chr16-75479364-C-T is described in ClinVar as Benign. ClinVar VariationId is 320612.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.086 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00687 (1046/152348) while in subpopulation SAS AF = 0.0257 (124/4828). AF 95% confidence interval is 0.022. There are 10 homozygotes in GnomAd4. There are 549 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
CHST6	NM_021615.5 link	c.465G>A	p.Arg155Arg	synonymous_variant	Exon 3 of 3	ENST00000332272.9	NP_067628.1
CHST6	NR_163480.1 link	n.733+2453G>A		intron_variant	Intron 3 of 3
CHST6	NR_163481.1 link	n.577+2453G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHST6	ENST00000332272.9 link	c.465G>A	p.Arg155Arg	synonymous_variant	Exon 3 of 3	3	NM_021615.5	ENSP00000328983.4

Frequencies

GnomAD3 genomes

AF:

0.00687

AC:

1046

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00113

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.0280

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.0257

Gnomad FIN

AF:

0.0175

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00735

Gnomad OTH

AF:

0.00669

GnomAD2 exomes

AF:

0.0106

AC:

2599

AN:

246150

AF XY:

0.0116

show subpopulations

Gnomad AFR exome

AF:

0.000832

Gnomad AMR exome

AF:

0.00256

Gnomad ASJ exome

AF:

0.0263

Gnomad EAS exome

AF:

0.000500

Gnomad FIN exome

AF:

0.0214

Gnomad NFE exome

AF:

0.00838

Gnomad OTH exome

AF:

0.00927

GnomAD4 exome

AF:

0.00812

AC:

11853

AN:

1460324

Hom.:

109

Cov.:

AF XY:

0.00876

AC XY:

6361

AN XY:

726542

show subpopulations

African (AFR)

AF:

0.000897

AC:

AN:

33462

American (AMR)

AF:

0.00277

AC:

124

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.0257

AC:

671

AN:

26104

East Asian (EAS)

AF:

0.000202

AC:

AN:

39690

South Asian (SAS)

AF:

0.0252

AC:

2174

AN:

86242

European-Finnish (FIN)

AF:

0.0186

AC:

974

AN:

52238

Middle Eastern (MID)

AF:

0.00832

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00654

AC:

7270

AN:

1111758

Other (OTH)

AF:

0.00918

AC:

554

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

915

1830

2745

3660

4575

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

272

544

816

1088

1360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00687

AC:

1046

AN:

152348

Hom.:

Cov.:

AF XY:

0.00737

AC XY:

549

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.00113

AC:

AN:

41588

American (AMR)

AF:

0.00320

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0280

AC:

AN:

3470

East Asian (EAS)

AF:

0.000964

AC:

AN:

5186

South Asian (SAS)

AF:

0.0257

AC:

124

AN:

4828

European-Finnish (FIN)

AF:

0.0175

AC:

186

AN:

10622

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00735

AC:

500

AN:

68024

Other (OTH)

AF:

0.00662

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

102

154

205

256

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00976

Hom.:

Bravo

AF:

0.00497

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.00643

EpiControl

AF:

0.00699

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Macular corneal dystrophy

Benign:2

Jan 13, 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.

Jan 24, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

CHST6-related disorder

Benign:1

Mar 14, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.1

(source)

DANN

Benign

0.83

PhyloP100

-0.086

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over