Variant 15-101177475-G-T 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.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

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=-0.88).

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. Variant chr15-101177475-G-T is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
CHSY1	NM_014918.5 linkuse as main transcript	c.2322C>A	p.Thr774Thr	synonymous_variant	3/3	ENST00000254190.4	NP_055733.2	Q86X52

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CHSY1	ENST00000254190.4 linkuse as main transcript	c.2322C>A	p.Thr774Thr	synonymous_variant	3/3	1	NM_014918.5	ENSP00000254190.3	Q86X52
CHSY1	ENST00000543813.2 linkuse as main transcript	n.*1637C>A		non_coding_transcript_exon_variant	3/3	2		ENSP00000496160.1	A0A2R8Y7B7
CHSY1	ENST00000543813.2 linkuse as main transcript	n.*1637C>A		3_prime_UTR_variant	3/3	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

GnomAD3 exomes

AF:

0.646

AC:

162025

AN:

250676

Hom.:

54002

AF XY:

0.640

AC XY:

86758

AN XY:

135528

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 SAS exome

AF:

0.688

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

Gnomad4 AFR exome

AF:

0.871

Gnomad4 AMR exome

AF:

0.675

Gnomad4 ASJ exome

AF:

0.540

Gnomad4 EAS exome

AF:

0.897

Gnomad4 SAS exome

AF:

0.686

Gnomad4 FIN exome

AF:

0.634

Gnomad4 NFE exome

AF:

0.564

Gnomad4 OTH exome

AF:

0.617

GnomAD4 genome

AF:

0.676

AC:

102811

AN:

152144

Hom.:

35972

Cov.:

AF XY:

0.683

AC XY:

50798

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.859

Gnomad4 AMR

AF:

0.671

Gnomad4 ASJ

AF:

0.517

Gnomad4 EAS

AF:

0.881

Gnomad4 SAS

AF:

0.695

Gnomad4 FIN

AF:

0.644

Gnomad4 NFE

AF:

0.564

Gnomad4 OTH

AF:

0.654

Alfa

AF:

0.607

Hom.:

16671

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

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 22, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.17

DANN

Benign

0.47

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