15-101177683-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014918.5(CHSY1):c.2114G>A(p.Arg705Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 1,614,080 control chromosomes in the GnomAD database, including 14,703 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 1082 hom., cov: 33)

Exomes 𝑓: 0.13 ( 13621 hom. )

Consequence

CHSY1
NM_014918.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.74

Publications

22 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: Labcorp Genetics (formerly Invitae), Orphanet, G2P

CHSY1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016215444).

BP6

Variant 15-101177683-C-T is Benign according to our data. Variant chr15-101177683-C-T is described in ClinVar as Benign. ClinVar VariationId is 1167689.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014918.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHSY1	NM_014918.5	MANE Select	c.2114G>A	p.Arg705Gln	missense	Exon 3 of 3	NP_055733.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHSY1	ENST00000254190.4	TSL:1 MANE Select	c.2114G>A	p.Arg705Gln	missense	Exon 3 of 3	ENSP00000254190.3	Q86X52
CHSY1	ENST00000968149.1		c.2108G>A	p.Arg703Gln	missense	Exon 3 of 3	ENSP00000638208.1
CHSY1	ENST00000543813.2	TSL:2	n.*1429G>A		non_coding_transcript_exon	Exon 3 of 3	ENSP00000496160.1	A0A2R8Y7B7

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

15333

AN:

152090

Hom.:

1083

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0261

Gnomad AMI

AF:

0.139

Gnomad AMR

AF:

0.0803

Gnomad ASJ

AF:

0.150

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0631

Gnomad FIN

AF:

0.173

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.147

Gnomad OTH

AF:

0.101

GnomAD2 exomes

AF:

0.107

AC:

26847

AN:

251454

AF XY:

0.109

show subpopulations

Gnomad AFR exome

AF:

0.0219

Gnomad AMR exome

AF:

0.0651

Gnomad ASJ exome

AF:

0.156

Gnomad EAS exome

AF:

0.000326

Gnomad FIN exome

AF:

0.169

Gnomad NFE exome

AF:

0.142

Gnomad OTH exome

AF:

0.118

GnomAD4 exome

AF:

0.131

AC:

190848

AN:

1461872

Hom.:

13621

Cov.:

AF XY:

0.129

AC XY:

93834

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.0231

AC:

772

AN:

33480

American (AMR)

AF:

0.0663

AC:

2966

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.153

AC:

3997

AN:

26136

East Asian (EAS)

AF:

0.000403

AC:

AN:

39700

South Asian (SAS)

AF:

0.0689

AC:

5941

AN:

86258

European-Finnish (FIN)

AF:

0.167

AC:

8929

AN:

53418

Middle Eastern (MID)

AF:

0.137

AC:

791

AN:

5768

European-Non Finnish (NFE)

AF:

0.144

AC:

160321

AN:

1111992

Other (OTH)

AF:

0.118

AC:

7115

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

11303

22607

33910

45214

56517

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5574

11148

16722

22296

27870

<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:

0.101

AC:

15330

AN:

152208

Hom.:

1082

Cov.:

AF XY:

0.101

AC XY:

7522

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.0261

AC:

1085

AN:

41556

American (AMR)

AF:

0.0802

AC:

1226

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.150

AC:

519

AN:

3470

East Asian (EAS)

AF:

0.00116

AC:

AN:

5184

South Asian (SAS)

AF:

0.0629

AC:

303

AN:

4816

European-Finnish (FIN)

AF:

0.173

AC:

1827

AN:

10572

Middle Eastern (MID)

AF:

0.187

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.147

AC:

9971

AN:

68008

Other (OTH)

AF:

0.100

AC:

211

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

696

1392

2088

2784

3480

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

170

340

510

680

850

<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:

0.122

Hom.:

3089

Bravo

AF:

0.0893

TwinsUK

AF:

0.156

AC:

577

ALSPAC

AF:

0.144

AC:

556

ESP6500AA

AF:

0.0275

AC:

121

ESP6500EA

AF:

0.142

AC:

1221

ExAC

AF:

0.105

AC:

12797

Asia WGS

AF:

0.0300

AC:

105

AN:

3478

EpiCase

AF:

0.144

EpiControl

AF:

0.139

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Temtamy preaxial brachydactyly syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.026

Eigen

Benign

0.0023

Eigen_PC

Benign

0.095

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.68

MetaRNN

Benign

0.0016

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

PhyloP100

1.7

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.95

REVEL

Benign

0.051

Sift

Benign

0.55

Sift4G

Benign

0.51

Polyphen

0.90

Vest4

0.042

MPC

0.37

ClinPred

0.013

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.063

gMVP

0.45

Mutation Taster

=91/9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over