rs3803423

chr15-101177901-G-Achr15-101177901-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_014918.5(CHSY1):c.1896C>T(p.Val632=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0167 in 1,614,172 control chromosomes in the GnomAD database, including 454 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (39 hom., cov: 33)
  • Exomes 𝑓: 0.016 (415 hom.)
• Consequence: CHSY1 NM_014918.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0910

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 15-101177901-G-A is Benign according to our data. Variant chr15-101177901-G-A is described in ClinVar as [Benign]. Clinvar id is 466171.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.091 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHSY1	NM_014918.5	c.1896C>T	p.Val632=	synonymous_variant	3/3	ENST00000254190.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHSY1	ENST00000254190.4	c.1896C>T	p.Val632=	synonymous_variant	3/3	1	NM_014918.5	P1
CHSY1	ENST00000543813.2	c.*1211C>T		3_prime_UTR_variant, NMD_transcript_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.0183 AC: 2786 AN: 152186 Hom.: 39 Cov.: 33

Gnomad AFR AF: 0.00890

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0358

Gnomad ASJ AF: 0.0256

Gnomad EAS AF: 0.0975

Gnomad SAS AF: 0.0174

Gnomad FIN AF: 0.0265

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0126

Gnomad OTH AF: 0.0225

GnomAD3 exomes AF: 0.0270 AC: 6788 AN: 251478 Hom.: 216 AF XY: 0.0249 AC XY: 3390 AN XY: 135912

Gnomad AFR exome AF: 0.00714

Gnomad AMR exome AF: 0.0555

Gnomad ASJ exome AF: 0.0317

Gnomad EAS exome AF: 0.101

Gnomad SAS exome AF: 0.0133

Gnomad FIN exome AF: 0.0276

Gnomad NFE exome AF: 0.0124

Gnomad OTH exome AF: 0.0257

GnomAD4 exome AF: 0.0165 AC: 24095 AN: 1461868 Hom.: 415 Cov.: 37 AF XY: 0.0161 AC XY: 11741 AN XY: 727230

Gnomad4 AFR exome AF: 0.00681

Gnomad4 AMR exome AF: 0.0543

Gnomad4 ASJ exome AF: 0.0308

Gnomad4 EAS exome AF: 0.0843

Gnomad4 SAS exome AF: 0.0135

Gnomad4 FIN exome AF: 0.0274

Gnomad4 NFE exome AF: 0.0119

Gnomad4 OTH exome AF: 0.0219

GnomAD4 genome AF: 0.0183 AC: 2792 AN: 152304 Hom.: 39 Cov.: 33 AF XY: 0.0193 AC XY: 1441 AN XY: 74488

Gnomad4 AFR AF: 0.00900

Gnomad4 AMR AF: 0.0359

Gnomad4 ASJ AF: 0.0256

Gnomad4 EAS AF: 0.0971

Gnomad4 SAS AF: 0.0176

Gnomad4 FIN AF: 0.0265

Gnomad4 NFE AF: 0.0126

Gnomad4 OTH AF: 0.0237

Alfa AF: 0.0128 Hom.: 18

Bravo AF: 0.0192

Asia WGS AF: 0.0510 AC: 177 AN: 3478

EpiCase AF: 0.0135

EpiControl AF: 0.0116

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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

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	-0.76
Cadd	Benign	1.0
Dann	Benign	0.69

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

Other links and lift over

dbSNP: rs3803423; hg19: chr15-101718106; COSMIC: COSV54251937; COSMIC: COSV54251937;