NM_014918.5:c.321-6152T>C

Variant names:

• chr15-101241729-A-G
• rs752092
• NM_014918.5:c.321-6152T>C

Variant summary

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

The NM_014918.5(CHSY1):​c.321-6152T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 152,046 control chromosomes in the GnomAD database, including 15,655 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 0.42 (15655 hom., cov: 32)
• Consequence: CHSY1 NM_014918.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.607
• Publications: 23 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: Labcorp Genetics (formerly Invitae), G2P, Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014918.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHSY1	NM_014918.5	MANE Select	c.321-6152T>C		intron	N/A	NP_055733.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHSY1	ENST00000254190.4	TSL:1 MANE Select	c.321-6152T>C		intron	N/A	ENSP00000254190.3	Q86X52
	CHSY1	ENST00000968149.1		c.321-6152T>C		intron	N/A	ENSP00000638208.1
	CHSY1	ENST00000559384.1	TSL:3	n.70+819T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64209 AN: 151928 Hom.: 15622 Cov.: 32

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.431

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

GnomAD4 genome AF: 0.423 AC: 64299 AN: 152046 Hom.: 15655 Cov.: 32 AF XY: 0.418 AC XY: 31041 AN XY: 74336

African (AFR) AF: 0.686 AC: 28447 AN: 41456

American (AMR) AF: 0.336 AC: 5131 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 1261 AN: 3470

East Asian (EAS) AF: 0.144 AC: 748 AN: 5188

South Asian (SAS) AF: 0.268 AC: 1290 AN: 4814

European-Finnish (FIN) AF: 0.312 AC: 3299 AN: 10576

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.335 AC: 22795 AN: 67948

Other (OTH) AF: 0.430 AC: 909 AN: 2112

Alfa AF: 0.363 Hom.: 48419

Bravo AF: 0.436

Asia WGS AF: 0.238 AC: 825 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.98
DANN	Benign	0.37
PhyloP100		-0.61
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: rs752092; hg19: chr15-101781934;