rs7176149

chr15-101251154-C-G

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.303G>C(p.Arg101=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 1,589,722 control chromosomes in the GnomAD database, including 24,785 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (5657 hom., cov: 32)
  • Exomes 𝑓: 0.15 (19128 hom.)
• Consequence: CHSY1 NM_014918.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0280

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=-0.6).
• BP6: Variant 15-101251154-C-G is Benign according to our data. Variant chr15-101251154-C-G is described in ClinVar as [Benign]. Clinvar id is 585674.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-101251154-C-G is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.028 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHSY1	NM_014918.5	c.303G>C	p.Arg101=	synonymous_variant	1/3	ENST00000254190.4
CHSY1	XM_011521364.3	c.303G>C	p.Arg101=	synonymous_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHSY1	ENST00000254190.4	c.303G>C	p.Arg101=	synonymous_variant	1/3	1	NM_014918.5	P1

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35744 AN: 151944 Hom.: 5655 Cov.: 32

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.0748

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.0992

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.248

GnomAD3 exomes AF: 0.151 AC: 31076 AN: 206342 Hom.: 2914 AF XY: 0.148 AC XY: 16817 AN XY: 113880

Gnomad AFR exome AF: 0.431

Gnomad AMR exome AF: 0.161

Gnomad ASJ exome AF: 0.132

Gnomad EAS exome AF: 0.0736

Gnomad SAS exome AF: 0.147

Gnomad FIN exome AF: 0.0864

Gnomad NFE exome AF: 0.140

Gnomad OTH exome AF: 0.159

GnomAD4 exome AF: 0.154 AC: 220715 AN: 1437660 Hom.: 19128 Cov.: 33 AF XY: 0.153 AC XY: 108859 AN XY: 713762

Gnomad4 AFR exome AF: 0.463

Gnomad4 AMR exome AF: 0.172

Gnomad4 ASJ exome AF: 0.138

Gnomad4 EAS exome AF: 0.0713

Gnomad4 SAS exome AF: 0.152

Gnomad4 FIN exome AF: 0.0977

Gnomad4 NFE exome AF: 0.148

Gnomad4 OTH exome AF: 0.172

GnomAD4 genome AF: 0.235 AC: 35782 AN: 152062 Hom.: 5657 Cov.: 32 AF XY: 0.232 AC XY: 17213 AN XY: 74330

Gnomad4 AFR AF: 0.451

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.0748

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.0992

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.245

Alfa AF: 0.189 Hom.: 683

Bravo AF: 0.256

Asia WGS AF: 0.130 AC: 452 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Temtamy preaxial brachydactyly syndrome Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 22, 2021	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Aug 10, 2018	- -
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	-0.60
Cadd	Benign	12
Dann	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs7176149; hg19: chr15-101791359; COSMIC: COSV54254479;