Variant rs76457230 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_014918.5(CHSY1):c.1473A>G(p.Gln491=) 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:3

Conservation

PhyloP100: 0.212

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 466169.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-101178324-T-C is described in Lovd as [Benign].

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/exons	MANE	UniProt
CHSY1	NM_014918.5 linkuse as main transcript	c.1473A>G	p.Gln491=	synonymous_variant	3/3	ENST00000254190.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHSY1	ENST00000254190.4 linkuse as main transcript	c.1473A>G	p.Gln491=	synonymous_variant	3/3	1	NM_014918.5	P1
CHSY1	ENST00000543813.2 linkuse as main transcript	c.*788A>G		3_prime_UTR_variant, NMD_transcript_variant	3/3	2

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

GnomAD3 exomes

AF:

0.0299

AC:

7516

AN:

251004

Hom.:

238

AF XY:

0.0272

AC XY:

3689

AN XY:

135682

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 SAS exome

AF:

0.0134

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

Gnomad4 AFR exome

AF:

0.0390

Gnomad4 AMR exome

AF:

0.0566

Gnomad4 ASJ exome

AF:

0.0308

Gnomad4 EAS exome

AF:

0.0927

Gnomad4 SAS exome

AF:

0.0138

Gnomad4 FIN exome

AF:

0.0274

Gnomad4 NFE exome

AF:

0.0118

Gnomad4 OTH exome

AF:

0.0246

GnomAD4 genome

AF:

0.0279

AC:

4242

AN:

152312

Hom.:

Cov.:

AF XY:

0.0284

AC XY:

2118

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0412

Gnomad4 AMR

AF:

0.0403

Gnomad4 ASJ

AF:

0.0256

Gnomad4 EAS

AF:

0.104

Gnomad4 SAS

AF:

0.0178

Gnomad4 FIN

AF:

0.0261

Gnomad4 NFE

AF:

0.0124

Gnomad4 OTH

AF:

0.0336

Alfa

AF:

0.0199

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:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 08, 2019	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 16, 2018	- -

Temtamy preaxial brachydactyly syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.73

DANN

Benign

0.39

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over