rs61740901

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.258A>C(p.Ala86Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0031 in 1,612,988 control chromosomes in the GnomAD database, including 104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 43 hom., cov: 33)

Exomes 𝑓: 0.0021 ( 61 hom. )

Consequence

CHST6
NM_021615.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.99

Publications

3 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=-0.95).

BP6

Variant 16-75479571-T-G is Benign according to our data. Variant chr16-75479571-T-G is described in ClinVar as Benign. ClinVar VariationId is 320613.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.99 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0126 (1916/152318) while in subpopulation AFR AF = 0.0398 (1655/41570). AF 95% confidence interval is 0.0382. There are 43 homozygotes in GnomAd4. There are 904 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 43 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHST6	NM_021615.5 link	c.258A>C	p.Ala86Ala	synonymous_variant	Exon 3 of 3	ENST00000332272.9	NP_067628.1	Q9GZX3
CHST6	NR_163480.1 link	n.733+2246A>C		intron_variant	Intron 3 of 3
CHST6	NR_163481.1 link	n.577+2246A>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHST6	ENST00000332272.9 link	c.258A>C	p.Ala86Ala	synonymous_variant	Exon 3 of 3	3	NM_021615.5	ENSP00000328983.4		Q9GZX3

Frequencies

GnomAD3 genomes

AF:

0.0126

AC:

1913

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0399

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00589

Gnomad ASJ

AF:

0.0340

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000413

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.0110

GnomAD2 exomes

AF:

0.00501

AC:

1250

AN:

249294

AF XY:

0.00412

show subpopulations

Gnomad AFR exome

AF:

0.0436

Gnomad AMR exome

AF:

0.00368

Gnomad ASJ exome

AF:

0.0330

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000553

Gnomad OTH exome

AF:

0.00525

GnomAD4 exome

AF:

0.00211

AC:

3080

AN:

1460670

Hom.:

Cov.:

AF XY:

0.00197

AC XY:

1429

AN XY:

726676

show subpopulations

African (AFR)

AF:

0.0414

AC:

1384

AN:

33470

American (AMR)

AF:

0.00389

AC:

174

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.0324

AC:

847

AN:

26112

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.000151

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52426

Middle Eastern (MID)

AF:

0.00243

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000288

AC:

320

AN:

1111874

Other (OTH)

AF:

0.00543

AC:

328

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

223

445

668

890

1113

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

168

224

280

<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:

0.0126

AC:

1916

AN:

152318

Hom.:

Cov.:

AF XY:

0.0121

AC XY:

904

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.0398

AC:

1655

AN:

41570

American (AMR)

AF:

0.00588

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0340

AC:

118

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000414

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000397

AC:

AN:

68018

Other (OTH)

AF:

0.0109

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

190

286

381

476

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:

0.00831

Hom.:

Bravo

AF:

0.0150

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.000818

EpiControl

AF:

0.000830

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Macular corneal dystrophy

Benign:2

Dec 19, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.027

(source)

DANN

Benign

0.46

PhyloP100

-4.0

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