rs117481449

Variant names:

• chr15-101235565-C-T
• rs117481449
• NM_014918.5:c.333G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_014918.5(CHSY1):​c.333G>A​(p.Lys111Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00541 in 1,610,168 control chromosomes in the GnomAD database, including 94 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0054 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0054 (86 hom.)
• Consequence: CHSY1 NM_014918.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.854
• Publications: 1 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 15-101235565-C-T is Benign according to our data. Variant chr15-101235565-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 534523.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.854 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0054 (822/152160) while in subpopulation AMR AF = 0.0293 (447/15266). AF 95% confidence interval is 0.027. There are 8 homozygotes in GnomAd4. There are 420 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

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.333G>A	p.Lys111Lys	synonymous	Exon 2 of 3	NP_055733.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHSY1	ENST00000254190.4	TSL:1 MANE Select	c.333G>A	p.Lys111Lys	synonymous	Exon 2 of 3	ENSP00000254190.3	Q86X52
	CHSY1	ENST00000968149.1		c.333G>A	p.Lys111Lys	synonymous	Exon 2 of 3	ENSP00000638208.1
	CHSY1	ENST00000559384.1	TSL:3	n.83G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.00538 AC: 818 AN: 152042 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00109

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0291

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.000662

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00420

Gnomad OTH AF: 0.00622

GnomAD2 exomes AF: 0.00977 AC: 2420 AN: 247778 AF XY: 0.00812

Gnomad AFR exome AF: 0.000687

Gnomad AMR exome AF: 0.0528

Gnomad ASJ exome AF: 0.00129

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000530

Gnomad NFE exome AF: 0.00397

Gnomad OTH exome AF: 0.00559

GnomAD4 exome AF: 0.00541 AC: 7895 AN: 1458008 Hom.: 86 Cov.: 32 AF XY: 0.00517 AC XY: 3749 AN XY: 725530

African (AFR) AF: 0.000657 AC: 22 AN: 33480

American (AMR) AF: 0.0499 AC: 2231 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00111 AC: 29 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00243 AC: 210 AN: 86250

European-Finnish (FIN) AF: 0.000584 AC: 29 AN: 49686

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5768

European-Non Finnish (NFE) AF: 0.00457 AC: 5080 AN: 1111900

Other (OTH) AF: 0.00474 AC: 286 AN: 60368

GnomAD4 genome AF: 0.00540 AC: 822 AN: 152160 Hom.: 8 Cov.: 32 AF XY: 0.00565 AC XY: 420 AN XY: 74366

African (AFR) AF: 0.00108 AC: 45 AN: 41514

American (AMR) AF: 0.0293 AC: 447 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00311 AC: 15 AN: 4818

European-Finnish (FIN) AF: 0.000662 AC: 7 AN: 10574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00420 AC: 286 AN: 68028

Other (OTH) AF: 0.00616 AC: 13 AN: 2112

Alfa AF: 0.00332 Hom.: 2

Bravo AF: 0.00720

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00453

EpiControl AF: 0.00385

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Temtamy preaxial brachydactyly syndrome (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	14
DANN	Benign	0.66
PhyloP100		0.85
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs117481449; hg19: chr15-101775770; COSMIC: COSV54252749; COSMIC: COSV54252749;