NM_014918.5:c.1473A>G

Variant names:

• chr15-101178324-T-C
• rs76457230
• NM_014918.5:c.1473A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_014918.5(CHSY1):​c.1473A>G​(p.Gln491Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0186 in 1,608,234 control chromosomes in the GnomAD database, including 550 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.028 (75 hom., cov: 33)
  • Exomes 𝑓: 0.018 (475 hom.)
• Consequence: CHSY1 NM_014918.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.212
• Publications: 6 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 15-101178324-T-C is Benign according to our data. Variant chr15-101178324-T-C is described in ClinVar as Benign. ClinVar VariationId is 466169.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.212 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0972 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.1473A>G	p.Gln491Gln	synonymous	Exon 3 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.1473A>G	p.Gln491Gln	synonymous	Exon 3 of 3	ENSP00000254190.3	Q86X52
	CHSY1	ENST00000968149.1		c.1467A>G	p.Gln489Gln	synonymous	Exon 3 of 3	ENSP00000638208.1
	CHSY1	ENST00000543813.2	TSL:2	n.*788A>G		non_coding_transcript_exon	Exon 3 of 3	ENSP00000496160.1	A0A2R8Y7B7

Frequencies

GnomAD3 genomes AF: 0.0277 AC: 4220 AN: 152194 Hom.: 74 Cov.: 33

Gnomad AFR AF: 0.0408

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0402

Gnomad ASJ AF: 0.0256

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.0178

Gnomad FIN AF: 0.0261

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0124

Gnomad OTH AF: 0.0325

GnomAD2 exomes AF: 0.0299 AC: 7516 AN: 251004 AF XY: 0.0272

Gnomad AFR exome AF: 0.0380

Gnomad AMR exome AF: 0.0575

Gnomad ASJ exome AF: 0.0318

Gnomad EAS exome AF: 0.110

Gnomad FIN exome AF: 0.0275

Gnomad NFE exome AF: 0.0124

Gnomad OTH exome AF: 0.0271

GnomAD4 exome AF: 0.0176 AC: 25606 AN: 1455922 Hom.: 475 Cov.: 37 AF XY: 0.0171 AC XY: 12346 AN XY: 722976

African (AFR) AF: 0.0390 AC: 1298 AN: 33272

American (AMR) AF: 0.0566 AC: 2517 AN: 44504

Ashkenazi Jewish (ASJ) AF: 0.0308 AC: 802 AN: 26062

East Asian (EAS) AF: 0.0927 AC: 3662 AN: 39512

South Asian (SAS) AF: 0.0138 AC: 1187 AN: 86178

European-Finnish (FIN) AF: 0.0274 AC: 1462 AN: 53364

Middle Eastern (MID) AF: 0.0156 AC: 90 AN: 5752

European-Non Finnish (NFE) AF: 0.0118 AC: 13110 AN: 1107204

Other (OTH) AF: 0.0246 AC: 1478 AN: 60074

GnomAD4 genome AF: 0.0279 AC: 4242 AN: 152312 Hom.: 75 Cov.: 33 AF XY: 0.0284 AC XY: 2118 AN XY: 74480

African (AFR) AF: 0.0412 AC: 1713 AN: 41574

American (AMR) AF: 0.0403 AC: 616 AN: 15298

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

East Asian (EAS) AF: 0.104 AC: 542 AN: 5188

South Asian (SAS) AF: 0.0178 AC: 86 AN: 4828

European-Finnish (FIN) AF: 0.0261 AC: 277 AN: 10614

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

European-Non Finnish (NFE) AF: 0.0124 AC: 842 AN: 68018

Other (OTH) AF: 0.0336 AC: 71 AN: 2116

Alfa AF: 0.0191 Hom.: 82

Bravo AF: 0.0301

Asia WGS AF: 0.0570 AC: 197 AN: 3478

EpiCase AF: 0.0132

EpiControl AF: 0.0116

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Temtamy preaxial brachydactyly syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.73
DANN	Benign	0.39
PhyloP100		0.21
Mutation Taster		=99/1	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: rs76457230; hg19: chr15-101718529; COSMIC: COSV54253632; COSMIC: COSV54253632;