rs12593811

Variant names:

• chr15-101181687-T-C
• rs12593811
• NM_014918.5:c.817-2707A>G

Variant summary

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

The NM_014918.5(CHSY1):​c.817-2707A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0179 in 152,300 control chromosomes in the GnomAD database, including 41 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 0.018 (41 hom., cov: 33)
• Consequence: CHSY1 NM_014918.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.378
• Publications: 3 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHSY1	NM_014918.5	c.817-2707A>G		intron_variant	Intron 2 of 2	ENST00000254190.4	NP_055733.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHSY1	ENST00000254190.4	c.817-2707A>G		intron_variant	Intron 2 of 2	1	NM_014918.5	ENSP00000254190.3
CHSY1	ENST00000543813.2	n.*132-2707A>G		intron_variant	Intron 2 of 2	2		ENSP00000496160.1
CHSY1	ENST00000560766.1	n.150-2707A>G		intron_variant	Intron 2 of 2	4
CHSY1	ENST00000561414.1	n.186-2707A>G		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes AF: 0.0178 AC: 2714 AN: 152182 Hom.: 41 Cov.: 33

Gnomad AFR AF: 0.00690

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0353

Gnomad ASJ AF: 0.0256

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.0174

Gnomad FIN AF: 0.0264

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0123

Gnomad OTH AF: 0.0224

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

GnomAD4 genome AF: 0.0179 AC: 2722 AN: 152300 Hom.: 41 Cov.: 33 AF XY: 0.0189 AC XY: 1407 AN XY: 74464

African (AFR) AF: 0.00703 AC: 292 AN: 41556

American (AMR) AF: 0.0354 AC: 541 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0256 AC: 89 AN: 3470

East Asian (EAS) AF: 0.104 AC: 541 AN: 5186

South Asian (SAS) AF: 0.0176 AC: 85 AN: 4828

European-Finnish (FIN) AF: 0.0264 AC: 280 AN: 10612

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0123 AC: 838 AN: 68028

Other (OTH) AF: 0.0236 AC: 50 AN: 2116

Alfa AF: 0.0180 Hom.: 33

Bravo AF: 0.0188

Asia WGS AF: 0.0530 AC: 183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.68
DANN	Benign	0.84
PhyloP100		-0.38
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: rs12593811; hg19: chr15-101721892;