15-101177475-G-T

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.2322C>A(p.Thr774Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 1,613,236 control chromosomes in the GnomAD database, including 299,583 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.68 ( 35972 hom., cov: 33)

Exomes 𝑓: 0.60 ( 263611 hom. )

Consequence

CHSY1
NM_014918.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.19

Publications

20 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=-0.88).

BP6

Variant 15-101177475-G-T is Benign according to our data. Variant chr15-101177475-G-T is described in ClinVar as [Benign]. Clinvar id is 672053.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.19 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHSY1	NM_014918.5 link	c.2322C>A	p.Thr774Thr	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.2322C>A	p.Thr774Thr	synonymous_variant	Exon 3 of 3	1	NM_014918.5	ENSP00000254190.3	Q86X52
CHSY1	ENST00000543813.2 link	n.*1637C>A		non_coding_transcript_exon_variant	Exon 3 of 3	2		ENSP00000496160.1	A0A2R8Y7B7
CHSY1	ENST00000543813.2 link	n.*1637C>A		3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000496160.1	A0A2R8Y7B7

Frequencies

GnomAD3 genomes

AF:

0.676

AC:

102715

AN:

152026

Hom.:

35928

Cov.:

show subpopulations

Gnomad AFR

AF:

0.859

Gnomad AMI

AF:

0.524

Gnomad AMR

AF:

0.670

Gnomad ASJ

AF:

0.517

Gnomad EAS

AF:

0.881

Gnomad SAS

AF:

0.696

Gnomad FIN

AF:

0.644

Gnomad MID

AF:

0.687

Gnomad NFE

AF:

0.564

Gnomad OTH

AF:

0.655

GnomAD2 exomes

AF:

0.646

AC:

162025

AN:

250676

AF XY:

0.640

show subpopulations

Gnomad AFR exome

AF:

0.869

Gnomad AMR exome

AF:

0.675

Gnomad ASJ exome

AF:

0.534

Gnomad EAS exome

AF:

0.878

Gnomad FIN exome

AF:

0.640

Gnomad NFE exome

AF:

0.569

Gnomad OTH exome

AF:

0.625

GnomAD4 exome

AF:

0.595

AC:

869586

AN:

1461092

Hom.:

263611

Cov.:

AF XY:

0.597

AC XY:

433587

AN XY:

726798

show subpopulations

African (AFR)

AF:

0.871

AC:

29141

AN:

33446

American (AMR)

AF:

0.675

AC:

30088

AN:

44606

Ashkenazi Jewish (ASJ)

AF:

0.540

AC:

14105

AN:

26112

East Asian (EAS)

AF:

0.897

AC:

35607

AN:

39696

South Asian (SAS)

AF:

0.686

AC:

59110

AN:

86104

European-Finnish (FIN)

AF:

0.634

AC:

33846

AN:

53416

Middle Eastern (MID)

AF:

0.624

AC:

3593

AN:

5760

European-Non Finnish (NFE)

AF:

0.564

AC:

626827

AN:

1111592

Other (OTH)

AF:

0.617

AC:

37269

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

18858

37715

56573

75430

94288

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.676

AC:

102811

AN:

152144

Hom.:

35972

Cov.:

AF XY:

0.683

AC XY:

50798

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.859

AC:

35678

AN:

41530

American (AMR)

AF:

0.671

AC:

10259

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.517

AC:

1795

AN:

3470

East Asian (EAS)

AF:

0.881

AC:

4561

AN:

5180

South Asian (SAS)

AF:

0.695

AC:

3355

AN:

4826

European-Finnish (FIN)

AF:

0.644

AC:

6793

AN:

10548

Middle Eastern (MID)

AF:

0.677

AC:

199

AN:

294

European-Non Finnish (NFE)

AF:

0.564

AC:

38312

AN:

67978

Other (OTH)

AF:

0.654

AC:

1381

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1634

3268

4903

6537

8171

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.612

Hom.:

17877

Bravo

AF:

0.685

Asia WGS

AF:

0.779

AC:

2705

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Temtamy preaxial brachydactyly syndrome

Benign:2

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Jun 14, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

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

-0.88

CADD

Benign

0.17

(source)

DANN

Benign

0.47

PhyloP100

-1.2

Mutation Taster

=98/2

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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15-101177475-G-T

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