rs329292

Variant names:

• chr15-101224776-C-T
• rs329292
• NM_014918.5:c.816+10306G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014918.5(CHSY1):​c.816+10306G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.84 in 152,226 control chromosomes in the GnomAD database, including 54,219 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.84 (54219 hom., cov: 33)
• Consequence: CHSY1 NM_014918.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502
• Publications: 5 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHSY1	NM_014918.5	c.816+10306G>A		intron_variant	Intron 2 of 2	ENST00000254190.4	NP_055733.2
CHSY1	XM_011521364.3	c.817-6568G>A		intron_variant	Intron 2 of 3		XP_011519666.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHSY1	ENST00000254190.4	c.816+10306G>A		intron_variant	Intron 2 of 2	1	NM_014918.5	ENSP00000254190.3
CHSY1	ENST00000543813.2	n.66+10306G>A		intron_variant	Intron 1 of 2	2		ENSP00000496160.1

Frequencies

GnomAD3 genomes AF: 0.839 AC: 127690 AN: 152108 Hom.: 54169 Cov.: 33

Gnomad AFR AF: 0.936

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.799

Gnomad ASJ AF: 0.867

Gnomad EAS AF: 0.562

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.827

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.828

Gnomad OTH AF: 0.842

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.840 AC: 127800 AN: 152226 Hom.: 54219 Cov.: 33 AF XY: 0.834 AC XY: 62053 AN XY: 74430

African (AFR) AF: 0.936 AC: 38885 AN: 41538

American (AMR) AF: 0.799 AC: 12206 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.867 AC: 3010 AN: 3472

East Asian (EAS) AF: 0.562 AC: 2913 AN: 5186

South Asian (SAS) AF: 0.621 AC: 2994 AN: 4822

European-Finnish (FIN) AF: 0.827 AC: 8767 AN: 10596

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.828 AC: 56282 AN: 68004

Other (OTH) AF: 0.842 AC: 1782 AN: 2116

Alfa AF: 0.840 Hom.: 20356

Bravo AF: 0.847

Asia WGS AF: 0.637 AC: 2216 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.3
DANN	Benign	0.54
PhyloP100		-0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs329292; hg19: chr15-101764981;