rs76457230

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_014918.5(CHSY1):c.1473A>G(p.Gln491Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0186 in 1,608,234 control chromosomes in the GnomAD database, including 550 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.028 ( 75 hom., cov: 33)

Exomes 𝑓: 0.018 ( 475 hom. )

Consequence

CHSY1
NM_014918.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.212

Publications

6 publications found

Variant links:

Genes affected

CHSY1 (HGNC:17198): (chondroitin sulfate synthase 1) This gene encodes a member of the chondroitin N-acetylgalactosaminyltransferase family. These enzymes possess dual glucuronyltransferase and galactosaminyltransferase activity and play critical roles in the biosynthesis of chondroitin sulfate, a glycosaminoglycan involved in many biological processes including cell proliferation and morphogenesis. Decreased expression of this gene may play a role in colorectal cancer, and mutations in this gene are a cause of temtamy preaxial brachydactyly syndrome. [provided by RefSeq, Dec 2011]

CHSY1 Gene-Disease associations (from GenCC):

temtamy preaxial brachydactyly syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet

CHSY1 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=-0.85).

BP6

Variant 15-101178324-T-C is Benign according to our data. Variant chr15-101178324-T-C is described in ClinVar as Benign. ClinVar VariationId is 466169.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.212 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHSY1	NM_014918.5 link	c.1473A>G	p.Gln491Gln	synonymous_variant	Exon 3 of 3	ENST00000254190.4	NP_055733.2	Q86X52

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CHSY1	ENST00000254190.4 link	c.1473A>G	p.Gln491Gln	synonymous_variant	Exon 3 of 3	1	NM_014918.5	ENSP00000254190.3	Q86X52
CHSY1	ENST00000543813.2 link	n.*788A>G		non_coding_transcript_exon_variant	Exon 3 of 3	2		ENSP00000496160.1	A0A2R8Y7B7
CHSY1	ENST00000543813.2 link	n.*788A>G		3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000496160.1	A0A2R8Y7B7

Frequencies

GnomAD3 genomes

AF:

0.0277

AC:

4220

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0408

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0402

Gnomad ASJ

AF:

0.0256

Gnomad EAS

AF:

0.105

Gnomad SAS

AF:

0.0178

Gnomad FIN

AF:

0.0261

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0124

Gnomad OTH

AF:

0.0325

GnomAD2 exomes

AF:

0.0299

AC:

7516

AN:

251004

AF XY:

0.0272

show subpopulations

Gnomad AFR exome

AF:

0.0380

Gnomad AMR exome

AF:

0.0575

Gnomad ASJ exome

AF:

0.0318

Gnomad EAS exome

AF:

0.110

Gnomad FIN exome

AF:

0.0275

Gnomad NFE exome

AF:

0.0124

Gnomad OTH exome

AF:

0.0271

GnomAD4 exome

AF:

0.0176

AC:

25606

AN:

1455922

Hom.:

475

Cov.:

AF XY:

0.0171

AC XY:

12346

AN XY:

722976

show subpopulations

African (AFR)

AF:

0.0390

AC:

1298

AN:

33272

American (AMR)

AF:

0.0566

AC:

2517

AN:

44504

Ashkenazi Jewish (ASJ)

AF:

0.0308

AC:

802

AN:

26062

East Asian (EAS)

AF:

0.0927

AC:

3662

AN:

39512

South Asian (SAS)

AF:

0.0138

AC:

1187

AN:

86178

European-Finnish (FIN)

AF:

0.0274

AC:

1462

AN:

53364

Middle Eastern (MID)

AF:

0.0156

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.0118

AC:

13110

AN:

1107204

Other (OTH)

AF:

0.0246

AC:

1478

AN:

60074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

1559

3118

4678

6237

7796

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

598

1196

1794

2392

2990

<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:

0.0279

AC:

4242

AN:

152312

Hom.:

Cov.:

AF XY:

0.0284

AC XY:

2118

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.0412

AC:

1713

AN:

41574

American (AMR)

AF:

0.0403

AC:

616

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0256

AC:

AN:

3470

East Asian (EAS)

AF:

0.104

AC:

542

AN:

5188

South Asian (SAS)

AF:

0.0178

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0261

AC:

277

AN:

10614

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0124

AC:

842

AN:

68018

Other (OTH)

AF:

0.0336

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

220

440

660

880

1100

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<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:

0.0191

Hom.:

Bravo

AF:

0.0301

Asia WGS

AF:

0.0570

AC:

197

AN:

3478

EpiCase

AF:

0.0132

EpiControl

AF:

0.0116

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

May 08, 2019

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 16, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Temtamy preaxial brachydactyly syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.73

(source)

DANN

Benign

0.39

PhyloP100

0.21

Mutation Taster

=99/1

polymorphism (auto)

(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