rs8043243

Variant names:

• chr15-101231248-C-T
• rs8043243
• NM_014918.5:c.816+3834G>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+3834G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 152,088 control chromosomes in the GnomAD database, including 15,333 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 0.43 (15333 hom., cov: 32)
• Consequence: CHSY1 NM_014918.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0940
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHSY1	NM_014918.5	c.816+3834G>A		intron_variant	Intron 2 of 2	ENST00000254190.4	NP_055733.2
CHSY1	XM_011521364.3	c.816+3834G>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+3834G>A		intron_variant	Intron 2 of 2	1	NM_014918.5	ENSP00000254190.3
CHSY1	ENST00000543813.2	n.66+3834G>A		intron_variant	Intron 1 of 2	2		ENSP00000496160.1

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64740 AN: 151970 Hom.: 15309 Cov.: 32

Gnomad AFR AF: 0.635

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.0335

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.428

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

GnomAD4 genome AF: 0.426 AC: 64808 AN: 152088 Hom.: 15333 Cov.: 32 AF XY: 0.421 AC XY: 31324 AN XY: 74344

African (AFR) AF: 0.635 AC: 26350 AN: 41470

American (AMR) AF: 0.318 AC: 4858 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1410 AN: 3472

East Asian (EAS) AF: 0.0335 AC: 174 AN: 5188

South Asian (SAS) AF: 0.295 AC: 1425 AN: 4824

European-Finnish (FIN) AF: 0.359 AC: 3786 AN: 10548

Middle Eastern (MID) AF: 0.551 AC: 161 AN: 292

European-Non Finnish (NFE) AF: 0.375 AC: 25472 AN: 67990

Other (OTH) AF: 0.425 AC: 896 AN: 2108

Alfa AF: 0.392 Hom.: 9026

Bravo AF: 0.430

Asia WGS AF: 0.192 AC: 667 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.4
DANN	Benign	0.65
PhyloP100		-0.094
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: rs8043243; hg19: chr15-101771453;