rs117481449

Positions:

• chr15-101235565-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_014918.5(CHSY1):​c.333G>A​(p.Lys111=) 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

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]

ACMG classification

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHSY1	NM_014918.5	c.333G>A	p.Lys111=	synonymous_variant	2/3	ENST00000254190.4	NP_055733.2
CHSY1	XM_011521364.3	c.333G>A	p.Lys111=	synonymous_variant	2/4		XP_011519666.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHSY1	ENST00000254190.4	c.333G>A	p.Lys111=	synonymous_variant	2/3	1	NM_014918.5	ENSP00000254190	P1
CHSY1	ENST00000559384.1	n.83G>A		non_coding_transcript_exon_variant	2/2	3

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

GnomAD3 exomes AF: 0.00977 AC: 2420 AN: 247778 Hom.: 61 AF XY: 0.00812 AC XY: 1092 AN XY: 134418

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 SAS exome AF: 0.00248

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

Gnomad4 AFR exome AF: 0.000657

Gnomad4 AMR exome AF: 0.0499

Gnomad4 ASJ exome AF: 0.00111

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00243

Gnomad4 FIN exome AF: 0.000584

Gnomad4 NFE exome AF: 0.00457

Gnomad4 OTH exome AF: 0.00474

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

Gnomad4 AFR AF: 0.00108

Gnomad4 AMR AF: 0.0293

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.000662

Gnomad4 NFE AF: 0.00420

Gnomad4 OTH AF: 0.00616

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

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 27, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Feb 20, 2019	- -

Temtamy preaxial brachydactyly syndrome Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 28, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Mar 28, 2022	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	14
DANN	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs117481449; hg19: chr15-101775770; COSMIC: COSV54252749; COSMIC: COSV54252749;